chr5-170808671-G-A

Position:

chr5-170808671-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014211.3(GABRP):c.751G>A(p.Val251Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000273 in 1,613,808 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

GABRP
NM_014211.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.39

Variant links:

Genes affected

GABRP (HGNC:4089): (gamma-aminobutyric acid type A receptor subunit pi) The gamma-aminobutyric acid (GABA) A receptor is a multisubunit chloride channel that mediates the fastest inhibitory synaptic transmission in the central nervous system. The subunit encoded by this gene is expressed in several non-neuronal tissues including the uterus and ovaries. This subunit can assemble with known GABA A receptor subunits, and the presence of this subunit alters the sensitivity of recombinant receptors to modulatory agents such as pregnanolone. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2014]

GABRP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2071454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GABRP	NM_014211.3 linkuse as main transcript	c.751G>A	p.Val251Ile	missense_variant	8/10	ENST00000265294.9	NP_055026.1
GABRP	NM_001291985.2 linkuse as main transcript	c.751G>A	p.Val251Ile	missense_variant	8/9		NP_001278914.1
GABRP	XM_024446012.2 linkuse as main transcript	c.751G>A	p.Val251Ile	missense_variant	8/10		XP_024301780.1
GABRP	XM_005265872.2 linkuse as main transcript	c.514G>A	p.Val172Ile	missense_variant	6/8		XP_005265929.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
GABRP	ENST00000265294.9 linkuse as main transcript	c.751G>A	p.Val251Ile	missense_variant	8/10	1	NM_014211.3	ENSP00000265294	P1
GABRP	ENST00000518525.5 linkuse as main transcript	c.751G>A	p.Val251Ile	missense_variant	9/11	5		ENSP00000430100	P1
GABRP	ENST00000519598.1 linkuse as main transcript	c.751G>A	p.Val251Ile	missense_variant	8/10	5		ENSP00000430772
GABRP	ENST00000519385.5 linkuse as main transcript	c.751G>A	p.Val251Ile	missense_variant	8/9	2		ENSP00000430727

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000477

AC:

AN:

251394

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000233

AC:

AN:

1461666

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000216

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.000217

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000987

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000576

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

Mar 06, 2023

The c.751G>A (p.V251I) alteration is located in exon 8 (coding exon 7) of the GABRP gene. This alteration results from a G to A substitution at nucleotide position 751, causing the valine (V) at amino acid position 251 to be replaced by an isoleucine (I). 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

0.079

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

T;T;.;.

Eigen

Benign

-0.13

Eigen_PC

Benign

0.014

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.88

.;D;D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.21

T;T;T;T

MetaSVM

Benign

-0.54

MutationAssessor

Benign

0.34

N;N;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.17

N;N;N;N

REVEL

Benign

0.27

Sift

Benign

0.13

T;T;T;T

Sift4G

Benign

0.78

T;T;T;T

Polyphen

0.98

D;D;B;.

Vest4

0.31

MVP

0.77

MPC

0.098

ClinPred

0.029

GERP RS

4.1

Varity_R

0.045

gMVP

0.43

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