rs140166160

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_020458.4(TTC7A):c.2170C>A(p.Gln724Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00688 in 1,609,952 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. Q724Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0045 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0071 ( 52 hom. )

Consequence

TTC7A
NM_020458.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.22

Publications

12 publications found

Variant links:

Genes affected

TTC7A (HGNC:19750): (tetratricopeptide repeat domain 7A) This gene encodes a protein containing tetratricopeptide repeats. Mutations in this gene disrupt intestinal development and can cause early onset inflammatory bowel disease and intestinal atresia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

TTC7A links:

STPG4 (HGNC:26850): (sperm-tail PG-rich repeat containing 4) Predicted to enable chromatin binding activity and histone binding activity. Predicted to be involved in DNA demethylation of male pronucleus and positive regulation of DNA demethylation. Predicted to act upstream of or within C-5 methylation of cytosine. Predicted to be located in cytoplasm and nucleus. Predicted to be active in female pronucleus; germinal vesicle; and male pronucleus. [provided by Alliance of Genome Resources, Apr 2022]

STPG4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004559338).

BP6

Variant 2-47060786-C-A is Benign according to our data. Variant chr2-47060786-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 528469.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0045 (686/152336) while in subpopulation NFE AF = 0.00723 (492/68026). AF 95% confidence interval is 0.0067. There are 4 homozygotes in GnomAd4. There are 341 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC7A	NM_020458.4 link	c.2170C>A	p.Gln724Lys	missense_variant	Exon 19 of 20	ENST00000319190.11	NP_065191.2	Q9ULT0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC7A	ENST00000319190.11 link	c.2170C>A	p.Gln724Lys	missense_variant	Exon 19 of 20	2	NM_020458.4	ENSP00000316699.5		Q9ULT0-1

Frequencies

GnomAD3 genomes

AF:

0.00451

AC:

686

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00181

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00510

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00559

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00723

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00499

AC:

1246

AN:

249682

AF XY:

0.00549

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.00381

Gnomad ASJ exome

AF:

0.00152

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000836

Gnomad NFE exome

AF:

0.00733

Gnomad OTH exome

AF:

0.00459

GnomAD4 exome

AF:

0.00713

AC:

10396

AN:

1457616

Hom.:

Cov.:

AF XY:

0.00706

AC XY:

5111

AN XY:

724414

show subpopulations

African (AFR)

AF:

0.00117

AC:

AN:

33422

American (AMR)

AF:

0.00366

AC:

163

AN:

44566

Ashkenazi Jewish (ASJ)

AF:

0.00166

AC:

AN:

25908

East Asian (EAS)

AF:

0.0000505

AC:

AN:

39608

South Asian (SAS)

AF:

0.00687

AC:

590

AN:

85872

European-Finnish (FIN)

AF:

0.000919

AC:

AN:

53312

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00821

AC:

9109

AN:

1108978

Other (OTH)

AF:

0.00653

AC:

393

AN:

60196

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

551

1101

1652

2202

2753

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

364

728

1092

1456

1820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00450

AC:

686

AN:

152336

Hom.:

Cov.:

AF XY:

0.00458

AC XY:

341

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.00180

AC:

AN:

41578

American (AMR)

AF:

0.00510

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00559

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.000565

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00723

AC:

492

AN:

68026

Other (OTH)

AF:

0.00284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

114

152

190

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00616

Hom.:

Bravo

AF:

0.00457

TwinsUK

AF:

0.0102

AC:

ALSPAC

AF:

0.00986

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00663

AC:

ExAC

AF:

0.00482

AC:

585

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00709

EpiControl

AF:

0.00706

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Sep 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

TTC7A: BP4, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Multiple gastrointestinal atresias

Benign:1

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.069

.;T;.

Eigen

Benign

0.039

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.017

MetaRNN

Benign

0.0046

T;T;T

MetaSVM

Benign

-0.64

MutationAssessor

Benign

1.4

.;L;.

PhyloP100

1.2

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.2

N;N;N

REVEL

Benign

0.15

Sift

Benign

0.20

T;T;T

Sift4G

Benign

0.61

T;T;T

Polyphen

0.12

B;B;.

Vest4

0.26

MVP

0.81

MPC

0.078

ClinPred

0.0082

GERP RS

5.8

Varity_R

0.11

gMVP

0.40

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over