Genetic Variant GATD1:p.Val157Ile (chr11-771408-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_182612.4(GATD1):c.469G>A(p.Val157Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000045 in 1,554,710 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00018 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

GATD1
NM_182612.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.532

Variant links:

Genes affected

GATD1 (HGNC:26616): (glutamine amidotransferase class 1 domain containing 1) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

GATD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03491038).

BP6

Variant 11-771408-C-T is Benign according to our data. Variant chr11-771408-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3519135.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATD1	NM_182612.4 link	c.469G>A	p.Val157Ile	missense_variant	Exon 6 of 8	ENST00000319863.13	NP_872418.1	Q8NB37-1B7Z1J9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATD1	ENST00000319863.13 link	c.469G>A	p.Val157Ile	missense_variant	Exon 6 of 8	1	NM_182612.4	ENSP00000321691.8		Q8NB37-1

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000814

AC:

AN:

184200

Hom.:

AF XY:

0.0000502

AC XY:

AN XY:

99590

show subpopulations

Gnomad AFR exome

AF:

0.000509

Gnomad AMR exome

AF:

0.0000784

Gnomad ASJ exome

AF:

0.000213

Gnomad EAS exome

AF:

0.0000611

Gnomad SAS exome

AF:

0.0000533

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000117

Gnomad OTH exome

AF:

0.000464

GnomAD4 exome

AF:

0.0000299

AC:

AN:

1402410

Hom.:

Cov.:

AF XY:

0.0000318

AC XY:

AN XY:

692352

show subpopulations

Gnomad4 AFR exome

AF:

0.000221

Gnomad4 AMR exome

AF:

0.0000547

Gnomad4 ASJ exome

AF:

0.000412

Gnomad4 EAS exome

AF:

0.000331

Gnomad4 SAS exome

AF:

0.0000525

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000369

Gnomad4 OTH exome

AF:

0.0000520

GnomAD4 genome

AF:

0.000184

AC:

AN:

152300

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.000529

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000151

ESP6500AA

AF:

0.000686

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000833

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jul 02, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.017

T;.;T;T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.80

T;T;T;T;T

M_CAP

Uncertain

0.26

MetaRNN

Benign

0.035

T;T;T;T;T

MetaSVM

Benign

-0.88

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.34

N;N;N;N;N

REVEL

Benign

0.17

Sift

Benign

0.47

T;T;T;T;T

Sift4G

Benign

0.52

T;T;T;T;T

Polyphen

0.063, 0.0

.;B;B;.;.

Vest4

0.18, 0.19, 0.21

MVP

0.19

MPC

0.21

ClinPred

0.0040

GERP RS

-1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.011

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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