dbSNP rs61738825: TTC7A:p.Ser100Ser (chr2-46950478-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020458.4(TTC7A):c.300C>T(p.Ser100Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0952 in 1,613,934 control chromosomes in the GnomAD database, including 8,074 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.078 ( 593 hom., cov: 32)

Exomes 𝑓: 0.097 ( 7481 hom. )

Consequence

TTC7A
NM_020458.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0150

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 2-46950478-C-T is Benign according to our data. Variant chr2-46950478-C-T is described in ClinVar as [Benign]. Clinvar id is 284146.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.015 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC7A	NM_020458.4 link	c.300C>T	p.Ser100Ser	synonymous_variant	Exon 2 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.300C>T	p.Ser100Ser	synonymous_variant	Exon 2 of 20	2	NM_020458.4	ENSP00000316699.5		Q9ULT0-1

Frequencies

GnomAD3 genomes

AF:

0.0783

AC:

11906

AN:

152006

Hom.:

592

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0344

Gnomad AMI

AF:

0.249

Gnomad AMR

AF:

0.0626

Gnomad ASJ

AF:

0.0946

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0768

Gnomad FIN

AF:

0.123

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.105

Gnomad OTH

AF:

0.0752

GnomAD3 exomes

AF:

0.0837

AC:

21038

AN:

251452

Hom.:

1143

AF XY:

0.0870

AC XY:

11818

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.0329

Gnomad AMR exome

AF:

0.0475

Gnomad ASJ exome

AF:

0.0891

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.0883

Gnomad FIN exome

AF:

0.117

Gnomad NFE exome

AF:

0.107

Gnomad OTH exome

AF:

0.0882

GnomAD4 exome

AF:

0.0969

AC:

141666

AN:

1461810

Hom.:

7481

Cov.:

AF XY:

0.0976

AC XY:

70985

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.0293

Gnomad4 AMR exome

AF:

0.0493

Gnomad4 ASJ exome

AF:

0.0916

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0885

Gnomad4 FIN exome

AF:

0.115

Gnomad4 NFE exome

AF:

0.105

Gnomad4 OTH exome

AF:

0.0914

GnomAD4 genome

AF:

0.0783

AC:

11909

AN:

152124

Hom.:

593

Cov.:

AF XY:

0.0795

AC XY:

5908

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.0343

Gnomad4 AMR

AF:

0.0624

Gnomad4 ASJ

AF:

0.0946

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.0775

Gnomad4 FIN

AF:

0.123

Gnomad4 NFE

AF:

0.105

Gnomad4 OTH

AF:

0.0739

Alfa

AF:

0.0954

Hom.:

371

Bravo

AF:

0.0709

Asia WGS

AF:

0.0310

AC:

109

AN:

3478

EpiCase

AF:

0.105

EpiControl

AF:

0.103

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Oct 13, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Multiple gastrointestinal atresias

Benign:1

Feb 03, 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

BayesDel_noAF

Benign

-0.54

CADD

Benign

6.6

DANN

Benign

0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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