14-100538096-G-T

Variant names:

• chr14-100538096-G-T
• rs781500772
• NM_001385089.1:c.1712C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001385089.1(BEGAIN):​c.1712C>A​(p.Ala571Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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. A571G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BEGAIN NM_001385089.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.34
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28346).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BEGAIN	NM_001385089.1	c.1712C>A	p.Ala571Asp	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.1712C>A	p.Ala571Asp	missense_variant	Exon 7 of 7	5	NM_001385089.1	ENSP00000451125.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1428834 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 708236

African (AFR) AF: 0.00 AC: 0 AN: 32390

American (AMR) AF: 0.00 AC: 0 AN: 40630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39164

South Asian (SAS) AF: 0.00 AC: 0 AN: 81682

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49878

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1097522

Other (OTH) AF: 0.00 AC: 0 AN: 58718

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.043	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	.;T;.;T
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.80	T;.;T;T
M_CAP	Uncertain	0.22	D
MetaRNN	Benign	0.28	T;T;T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.3	.;M;.;M
PhyloP100		3.3
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-2.2	.;N;.;N
REVEL	Benign	0.14
Sift	Uncertain	0.0030	.;D;.;D
Sift4G	Benign	0.18	.;T;.;T
Polyphen		0.96	.;D;.;D
Vest4		0.37, 0.31
MutPred		0.23		.;Gain of catalytic residue at M550 (P = 0);.;Gain of catalytic residue at M550 (P = 0);
MVP		0.22
MPC		1.5
ClinPred		0.94	D
GERP RS		3.7
Varity_R		0.36
gMVP		0.47
Mutation Taster		=72/28	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: rs781500772; hg19: chr14-101004433;