rs117304542

Positions:

• chr2-47005985-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_020458.4(TTC7A):​c.1129C>G​(p.Gln377Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00384 in 1,613,960 control chromosomes in the GnomAD database, including 174 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0030 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0039 (165 hom.)
• Consequence: TTC7A NM_020458.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 6.08

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0039553344).
• BP6: Variant 2-47005985-C-G is Benign according to our data. Variant chr2-47005985-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 445493.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00296 (450/152086) while in subpopulation SAS AF= 0.0461 (222/4812). AF 95% confidence interval is 0.0412. There are 9 homozygotes in gnomad4. There are 260 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC7A	NM_020458.4	c.1129C>G	p.Gln377Glu	missense_variant	9/20	ENST00000319190.11	NP_065191.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC7A	ENST00000319190.11	c.1129C>G	p.Gln377Glu	missense_variant	9/20	2	NM_020458.4	ENSP00000316699.5

Frequencies

GnomAD3 genomes AF: 0.00297 AC: 452 AN: 151968 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00210

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0330

Gnomad SAS AF: 0.0465

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00787 AC: 1978 AN: 251408 Hom.: 46 AF XY: 0.00943 AC XY: 1281 AN XY: 135892

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000173

Gnomad ASJ exome AF: 0.000893

Gnomad EAS exome AF: 0.0328

Gnomad SAS exome AF: 0.0421

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000334

Gnomad OTH exome AF: 0.00489

GnomAD4 exome AF: 0.00393 AC: 5747 AN: 1461874 Hom.: 165 Cov.: 31 AF XY: 0.00508 AC XY: 3697 AN XY: 727232

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.000179

Gnomad4 ASJ exome AF: 0.000727

Gnomad4 EAS exome AF: 0.0417

Gnomad4 SAS exome AF: 0.0412

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000189

Gnomad4 OTH exome AF: 0.00479

GnomAD4 genome AF: 0.00296 AC: 450 AN: 152086 Hom.: 9 Cov.: 32 AF XY: 0.00350 AC XY: 260 AN XY: 74306

Gnomad4 AFR AF: 0.000241

Gnomad4 AMR AF: 0.00210

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0329

Gnomad4 SAS AF: 0.0461

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00474

Alfa AF: 0.000600 Hom.: 0

Bravo AF: 0.00179

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00847 AC: 1028

Asia WGS AF: 0.0260 AC: 92 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2024	TTC7A: BP4, BS1, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	May 30, 2017	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Dec 10, 2021

- -

Multiple gastrointestinal atresias Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Benign	0.90
DEOGEN2	Benign	0.095	.;T;.
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.22
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.80	T;T;T
MetaRNN	Benign	0.0040	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	.;L;L
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Benign	0.041
Sift	Benign	0.31	T;T;T
Sift4G	Uncertain	0.016	D;D;D
Polyphen		0.010	B;B;.
Vest4		0.46
MVP		0.34
MPC		0.090
ClinPred		0.016	T
GERP RS		4.0
Varity_R		0.066
gMVP		0.24

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

Other links and lift over

dbSNP: rs117304542; hg19: chr2-47233124;