Variant 7-93906837-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_021955.5(GNGT1):c.91A>T(p.Met31Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000102 in 1,570,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

GNGT1
NM_021955.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.429

Variant links:

Genes affected

GNGT1 (HGNC:4411): (G protein subunit gamma transducin 1) This gene encodes the gamma subunit of transducin, a guanine nucleotide-binding protein (G protein) that is found in rod outer segments. Transducin, also known as GMPase, mediates the activation of a cyclic GTP-specific (guanosine monophosphate) phosphodiesterase by rhodopsin. [provided by RefSeq, Jul 2016]

GNGT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1303088).

BS2

High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNGT1	NM_021955.5 linkuse as main transcript	c.91A>T	p.Met31Leu	missense_variant	2/3	ENST00000248572.10	NP_068774.1	P63211
GNGT1	NM_001329426.2 linkuse as main transcript	c.91A>T	p.Met31Leu	missense_variant	2/3		NP_001316355.1	P63211

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNGT1	ENST00000248572.10 linkuse as main transcript	c.91A>T	p.Met31Leu	missense_variant	2/3	1	NM_021955.5	ENSP00000248572.5		P63211

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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:

0.00000426

AC:

AN:

234824

Hom.:

AF XY:

0.00000785

AC XY:

AN XY:

127432

show subpopulations

Gnomad AFR exome

AF:

0.0000663

Gnomad AMR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000564

AC:

AN:

1418630

Hom.:

Cov.:

AF XY:

0.00000283

AC XY:

AN XY:

707350

show subpopulations

Gnomad4 AFR exome

AF:

0.000253

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 13, 2024

The c.91A>T (p.M31L) alteration is located in exon 2 (coding exon 1) of the GNGT1 gene. This alteration results from a A to T substitution at nucleotide position 91, causing the methionine (M) at amino acid position 31 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.034

T;T;T;T;T

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.21

.;.;T;.;T

M_CAP

Benign

0.0058

MetaRNN

Benign

0.13

T;T;T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.46

PROVEAN

Benign

-2.1

N;N;N;N;N

REVEL

Benign

0.034

Sift

Benign

0.078

T;T;T;T;T

Sift4G

Benign

0.49

T;T;T;T;T

Polyphen

0.0

.;B;B;.;.

Vest4

0.28

MutPred

0.38

Loss of ubiquitination at K35 (P = 0.0755);Loss of ubiquitination at K35 (P = 0.0755);Loss of ubiquitination at K35 (P = 0.0755);Loss of ubiquitination at K35 (P = 0.0755);Loss of ubiquitination at K35 (P = 0.0755);

MVP

0.41

MPC

0.0067

ClinPred

0.058

GERP RS

3.3

Varity_R

0.13

gMVP

0.23

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