rs114202807

Positions:

chr2-47011380-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2BP4_StrongBP6_Very_StrongBS1

The NM_020458.4(TTC7A):c.1337C>T(p.Ser446Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00037 in 1,612,450 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

TTC7A
NM_020458.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.48

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:

TTC7A (HGNC:):

TTC7A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.008100599).

BP6

Variant 2-47011380-C-T is Benign according to our data. Variant chr2-47011380-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 528475.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00194 (296/152314) while in subpopulation AFR AF= 0.00671 (279/41572). AF 95% confidence interval is 0.00606. There are 1 homozygotes in gnomad4. There are 143 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC7A	NM_020458.4 linkuse as main transcript	c.1337C>T	p.Ser446Leu	missense_variant	11/20	ENST00000319190.11	NP_065191.2	Q9ULT0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC7A	ENST00000319190.11 linkuse as main transcript	c.1337C>T	p.Ser446Leu	missense_variant	11/20	2	NM_020458.4	ENSP00000316699.5		Q9ULT0-1

Frequencies

GnomAD3 genomes

AF:

0.00194

AC:

296

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00673

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000464

AC:

116

AN:

249764

Hom.:

AF XY:

0.000303

AC XY:

AN XY:

135094

show subpopulations

Gnomad AFR exome

AF:

0.00641

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000206

AC:

301

AN:

1460136

Hom.:

Cov.:

AF XY:

0.000180

AC XY:

131

AN XY:

726452

show subpopulations

Gnomad4 AFR exome

AF:

0.00750

Gnomad4 AMR exome

AF:

0.000313

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.0000386

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.000248

GnomAD4 genome

AF:

0.00194

AC:

296

AN:

152314

Hom.:

Cov.:

AF XY:

0.00192

AC XY:

143

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00671

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000459

Hom.:

Bravo

AF:

0.00209

ESP6500AA

AF:

0.00613

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000610

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

TTC7A-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 08, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Multiple gastrointestinal atresias

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 16, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

.;T;.

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.84

T;D;D

M_CAP

Benign

0.025

MetaRNN

Benign

0.0081

T;T;T

MetaSVM

Benign

-0.71

MutationAssessor

Benign

0.76

.;N;N

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-3.4

D;D;D

REVEL

Benign

0.098

Sift

Benign

0.040

D;D;D

Sift4G

Benign

0.11

T;T;T

Polyphen

0.73

P;P;.

Vest4

0.43

MVP

0.58

MPC

0.15

ClinPred

0.046

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.18

gMVP

0.10

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over