rs114276698

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_020458.4(TTC7A):c.1348G>A(p.Val450Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00193 in 1,611,706 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0020 ( 2 hom. )

Consequence

TTC7A
NM_020458.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.876

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.018479526).

BP6

Variant 2-47011391-G-A is Benign according to our data. Variant chr2-47011391-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 528467.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-47011391-G-A is described in Lovd as [Likely_benign]. Variant chr2-47011391-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00133 (203/152266) while in subpopulation NFE AF= 0.00226 (154/68016). AF 95% confidence interval is 0.00197. There are 0 homozygotes in gnomad4. There are 94 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC7A	NM_020458.4 link	c.1348G>A	p.Val450Met	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 link	c.1348G>A	p.Val450Met	missense_variant	11/20	2	NM_020458.4	ENSP00000316699.5		Q9ULT0-1

Frequencies

GnomAD3 genomes

AF:

0.00134

AC:

204

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00228

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00157

AC:

392

AN:

249268

Hom.:

AF XY:

0.00154

AC XY:

208

AN XY:

134890

show subpopulations

Gnomad AFR exome

AF:

0.000617

Gnomad AMR exome

AF:

0.000814

Gnomad ASJ exome

AF:

0.00199

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000753

Gnomad FIN exome

AF:

0.000149

Gnomad NFE exome

AF:

0.00259

Gnomad OTH exome

AF:

0.00213

GnomAD4 exome

AF:

0.00200

AC:

2913

AN:

1459440

Hom.:

Cov.:

AF XY:

0.00194

AC XY:

1409

AN XY:

726118

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.000761

Gnomad4 ASJ exome

AF:

0.00287

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000893

Gnomad4 FIN exome

AF:

0.000585

Gnomad4 NFE exome

AF:

0.00232

Gnomad4 OTH exome

AF:

0.00154

GnomAD4 genome

AF:

0.00133

AC:

203

AN:

152266

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000530

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00260

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00226

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00210

Hom.:

Bravo

AF:

0.00138

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00291

AC:

ExAC

AF:

0.00166

AC:

202

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00164

EpiControl

AF:

0.00208

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:6

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 22, 2021	This variant is associated with the following publications: (PMID: 28930861) -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

TTC7A-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 07, 2024

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

Multiple gastrointestinal atresias

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 28, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

.;T;.

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Benign

0.48

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.018

T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.8

.;L;L

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.20

Sift

Benign

0.049

D;D;D

Sift4G

Uncertain

0.031

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.71

MVP

0.41

MPC

0.31

ClinPred

0.010

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.039

gMVP

0.30

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