chr14-100538397-C-G

Variant names:

• chr14-100538397-C-G
• rs2030938843
• NM_001385089.1:c.1411G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001385089.1(BEGAIN):​c.1411G>C​(p.Ala471Pro) 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. 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)
• Consequence: BEGAIN NM_001385089.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.02
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08442229).

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.1411G>C	p.Ala471Pro	missense	Exon 7 of 7	NP_001372018.1	G3V3A2
	BEGAIN	NM_001385085.1		c.1501G>C	p.Ala501Pro	missense	Exon 8 of 8	NP_001372014.1
	BEGAIN	NM_001385086.1		c.1483G>C	p.Ala495Pro	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.1411G>C	p.Ala471Pro	missense	Exon 7 of 7	ENSP00000451125.2	G3V3A2
	BEGAIN	ENST00000355173.7	TSL:1	c.1354G>C	p.Ala452Pro	missense	Exon 7 of 7	ENSP00000347301.2	Q9BUH8
	BEGAIN	ENST00000557378.6	TSL:1	c.1354G>C	p.Ala452Pro	missense	Exon 6 of 6	ENSP00000450722.2	Q9BUH8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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	0.077
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	7.9
DANN	Benign	0.96
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.0
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.0080
Sift	Benign	0.13	T
Sift4G	Benign	0.30	T
Polyphen		0.13	B
Vest4		0.091
MutPred		0.20		Gain of catalytic residue at G453 (P = 4e-04)
MVP		0.17
MPC		0.59
ClinPred		0.10	T
GERP RS		-0.56
Varity_R		0.095
gMVP		0.19
Mutation Taster		=96/4	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: rs2030938843; hg19: chr14-101004734;