14-100538237-C-G

Variant names:

• chr14-100538237-C-G
• rs764209715
• NM_001385089.1:c.1571G>C

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.90
• Publications: 0 publications found

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]

LOC124903382 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 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	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	c.1571G>C	p.Arg524Pro	missense_variant	Exon 7 of 7	5	NM_001385089.1	ENSP00000451125.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1415762 Hom.: 0 Cov.: 31 AF XY: 0.00000142 AC XY: 1 AN XY: 702402

African (AFR) AF: 0.00 AC: 0 AN: 32074

American (AMR) AF: 0.00 AC: 0 AN: 40456

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24498

East Asian (EAS) AF: 0.00 AC: 0 AN: 38464

South Asian (SAS) AF: 0.00 AC: 0 AN: 81584

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38236

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5562

European-Non Finnish (NFE) AF: 0.00000182 AC: 2 AN: 1096232

Other (OTH) AF: 0.00 AC: 0 AN: 58656

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

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	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	.;T;.;T
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.83	T;.;T;T
M_CAP	Pathogenic	0.66	D
MetaRNN	Uncertain	0.50	T;T;T;T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	1.7	.;L;.;L
PhyloP100		1.9
PrimateAI	Pathogenic	0.89	D
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	D
GERP RS		4.7
Varity_R		0.37
gMVP		0.27
Mutation Taster		=68/32	polymorphism

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

Other links and lift over

dbSNP: rs764209715; hg19: chr14-101004574;