NM_001385089.1:c.1165C>T

Variant names:

• chr14-100538643-G-A
• rs775701649
• NM_001385089.1:c.1165C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001385089.1(BEGAIN):​c.1165C>T​(p.Arg389Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,397,426 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: BEGAIN NM_001385089.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.30
• 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385089.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BEGAIN	NM_001385089.1	MANE Select	c.1165C>T	p.Arg389Trp	missense	Exon 7 of 7	NP_001372018.1	G3V3A2
	BEGAIN	NM_001385085.1		c.1255C>T	p.Arg419Trp	missense	Exon 8 of 8	NP_001372014.1
	BEGAIN	NM_001385086.1		c.1237C>T	p.Arg413Trp	missense	Exon 8 of 8	NP_001372015.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BEGAIN	ENST00000554140.3	TSL:5 MANE Select	c.1165C>T	p.Arg389Trp	missense	Exon 7 of 7	ENSP00000451125.2	G3V3A2
	BEGAIN	ENST00000355173.7	TSL:1	c.1108C>T	p.Arg370Trp	missense	Exon 7 of 7	ENSP00000347301.2	Q9BUH8
	BEGAIN	ENST00000557378.6	TSL:1	c.1108C>T	p.Arg370Trp	missense	Exon 6 of 6	ENSP00000450722.2	Q9BUH8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.16e-7 AC: 1 AN: 1397426 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 689086

African (AFR) AF: 0.00 AC: 0 AN: 31658

American (AMR) AF: 0.00 AC: 0 AN: 35648

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25006

East Asian (EAS) AF: 0.0000279 AC: 1 AN: 35904

South Asian (SAS) AF: 0.00 AC: 0 AN: 79266

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47900

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5670

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078496

Other (OTH) AF: 0.00 AC: 0 AN: 57878

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.50	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.22	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.3
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.54
MutPred		0.57		Gain of catalytic residue at M372 (P = 0.0012)
MVP		0.41
MPC		1.3
ClinPred		0.95	D
GERP RS		0.34
Varity_R		0.58
gMVP		0.72
Mutation Taster		=81/19	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: rs775701649; hg19: chr14-101004980;