14-100538649-A-G

Position:

• chr14-100538649-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001385089.1(BEGAIN):​c.1159T>C​(p.Phe387Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 4.54

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32286483).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BEGAIN	NM_001385089.1	c.1159T>C	p.Phe387Leu	missense_variant	7/7	ENST00000554140.3	NP_001372018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BEGAIN	ENST00000554140.3	c.1159T>C	p.Phe387Leu	missense_variant	7/7	5	NM_001385089.1	ENSP00000451125.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 07, 2024

The c.1102T>C (p.F368L) alteration is located in exon 6 (coding exon 6) of the BEGAIN gene. This alteration results from a T to C substitution at nucleotide position 1102, causing the phenylalanine (F) at amino acid position 368 to be replaced by a leucine (L). 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	Pathogenic	0.83
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.038	.;T;.;T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.76	T;.;T;T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.32	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	.;L;.;L
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.0	.;D;.;D
REVEL	Benign	0.19
Sift	Uncertain	0.0050	.;D;.;D
Sift4G	Uncertain	0.017	.;D;.;D
Polyphen		0.86	.;P;.;P
Vest4		0.18, 0.17
MutPred		0.32		.;Gain of catalytic residue at R370 (P = 0.0012);.;Gain of catalytic residue at R370 (P = 0.0012);
MVP		0.36
MPC		0.85
ClinPred		0.76	D
GERP RS		4.2
Varity_R		0.29
gMVP		0.62

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-101004986;