dbSNP rs764209715: BEGAIN:p.Arg524Pro (chr14-100538237-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001385089.1(BEGAIN):c.1571G>C(p.Arg524Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,415,762 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R524H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

BEGAIN
NM_001385089.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.90

Variant links:

Genes affected

BEGAIN (HGNC:24163): (brain enriched guanylate kinase associated) Predicted to be involved in regulation of postsynaptic neurotransmitter receptor activity. Predicted to act upstream of or within evoked excitatory postsynaptic potential. Predicted to be located in dendrite; nucleus; and presynapse. Predicted to be active in glutamatergic synapse and postsynapse. [provided by Alliance of Genome Resources, Apr 2022]

BEGAIN links:

LOC124903382 (HGNC:):

LOC124903382 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BEGAIN	NM_001385089.1 link	c.1571G>C	p.Arg524Pro	missense_variant	Exon 7 of 7	ENST00000554140.3	NP_001372018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BEGAIN	ENST00000554140.3 link	c.1571G>C	p.Arg524Pro	missense_variant	Exon 7 of 7	5	NM_001385089.1	ENSP00000451125.2		G3V3A2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000141

AC:

AN:

1415762

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

702402

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000182

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.0099

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

.;T;.;T

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.83

T;.;T;T

M_CAP

Pathogenic

0.66

MetaRNN

Uncertain

0.50

T;T;T;T

MetaSVM

Benign

-0.62

MutationAssessor

Benign

1.7

.;L;.;L

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-1.6

.;N;.;N

REVEL

Benign

0.13

Sift

Benign

0.099

.;T;.;T

Sift4G

Benign

0.30

.;T;.;T

Polyphen

0.98

.;D;.;D

Vest4

0.19, 0.22

MutPred

0.21

.;Gain of catalytic residue at G504 (P = 0.0014);.;Gain of catalytic residue at G504 (P = 0.0014);

MVP

0.19

MPC

1.4

ClinPred

0.88

GERP RS

4.7

Varity_R

0.37

gMVP

0.27

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over