Variant 17-29575813-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_014030.4(GIT1):c.1751C>T(p.Thr584Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,612,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

GIT1
NM_014030.4 missense, splice_region

Scores

Splicing: ADA: 0.005552

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.713

Variant links:

Genes affected

GIT1 (HGNC:4272): (GIT ArfGAP 1) Enables gamma-tubulin binding activity. Involved in positive regulation of microtubule nucleation and regulation of cytokinesis. Located in several cellular components, including focal adhesion; microtubule cytoskeleton; and mitochondrion. Implicated in attention deficit hyperactivity disorder. Biomarker of Huntington's disease. [provided by Alliance of Genome Resources, Apr 2022]

GIT1 links:

GIT1 (HGNC:):

GIT1 links:

TP53I13 (HGNC:25102): (tumor protein p53 inducible protein 13) Involved in several processes, including negative regulation of cell cycle; response to UV; and response to xenobiotic stimulus. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TP53I13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.046678185).

BS2

High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GIT1	NM_014030.4 linkuse as main transcript	c.1751C>T	p.Thr584Met	missense_variant, splice_region_variant	16/20	ENST00000225394.8	NP_054749.2	Q9Y2X7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GIT1	ENST00000225394.8 linkuse as main transcript	c.1751C>T	p.Thr584Met	missense_variant, splice_region_variant	16/20	1	NM_014030.4	ENSP00000225394.3		Q9Y2X7-1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000244

AC:

AN:

246320

Hom.:

AF XY:

0.0000299

AC XY:

AN XY:

133898

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000986

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000270

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000288

AC:

AN:

1460500

Hom.:

Cov.:

AF XY:

0.0000317

AC XY:

AN XY:

726560

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000813

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000315

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000302

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 05, 2023

The c.1778C>T (p.T593M) alteration is located in exon 17 (coding exon 17) of the GIT1 gene. This alteration results from a C to T substitution at nucleotide position 1778, causing the threonine (T) at amino acid position 593 to be replaced by a methionine (M). 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

0.070

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.14

T;.;.;.;T

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.76

T;T;T;T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.047

T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.69

N;.;.;.;.

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.77

N;N;.;.;.

REVEL

Benign

0.12

Sift

Benign

0.061

T;T;.;.;.

Sift4G

Benign

0.18

T;T;T;T;T

Polyphen

0.017

B;B;.;.;.

Vest4

0.15

MVP

0.39

MPC

0.21

ClinPred

0.043

GERP RS

2.0

Varity_R

0.020

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0056

dbscSNV1_RF

Benign

0.11

SpliceAI score (max)

0.010

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