Genetic Variant NM_001385089.1:c.1241C>A (chr14-100538567-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001385089.1(BEGAIN):c.1241C>A(p.Pro414Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000216 in 1,391,284 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

BEGAIN
NM_001385089.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.08

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.121759325).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BEGAIN	NM_001385089.1 link	c.1241C>A	p.Pro414Gln	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.1241C>A	p.Pro414Gln	missense_variant	Exon 7 of 7	5	NM_001385089.1	ENSP00000451125.2		G3V3A2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000695

AC:

AN:

143984

AF XY:

0.0000130

show subpopulations

Gnomad AFR exome

AF:

0.000118

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000216

AC:

AN:

1391284

Hom.:

Cov.:

AF XY:

0.00000438

AC XY:

AN XY:

685236

show subpopulations

African (AFR)

AF:

0.0000934

AC:

AN:

32118

American (AMR)

AF:

0.00

AC:

AN:

34754

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23346

East Asian (EAS)

AF:

0.00

AC:

AN:

37446

South Asian (SAS)

AF:

0.00

AC:

AN:

76394

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47548

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5544

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1076614

Other (OTH)

AF:

0.00

AC:

AN:

57520

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 22, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1184C>A (p.P395Q) alteration is located in exon 6 (coding exon 6) of the BEGAIN gene. This alteration results from a C to A substitution at nucleotide position 1184, causing the proline (P) at amino acid position 395 to be replaced by a glutamine (Q). 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

0.18

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.012

.;T;.;T

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.69

T;.;T;T

M_CAP

Benign

0.036

MetaRNN

Benign

0.12

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

.;N;.;N

PhyloP100

2.1

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.8

.;N;.;N

REVEL

Benign

0.048

Sift

Benign

0.17

.;T;.;T

Sift4G

Benign

0.39

.;T;.;T

Polyphen

0.018

.;B;.;B

Vest4

0.097, 0.11

MutPred

0.35

.;Gain of catalytic residue at N396 (P = 0.0126);.;Gain of catalytic residue at N396 (P = 0.0126);

MVP

0.11

MPC

0.46

ClinPred

0.025

GERP RS

2.4

Varity_R

0.11

gMVP

0.28

Mutation Taster

=97/3

polymorphism

(source)

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

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NM_001385089.1:c.1241C>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over