rs780718553

Variant names:

• chr14-100538198-C-G
• rs780718553
• NM_001385089.1:c.1610G>C

Your query was ambiguous. Multiple possible variants found:

• chr14-100538198-C-G
• chr14-100538198-C-T
• chr14-100538198-C-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001385089.1(BEGAIN):​c.1610G>C​(p.Gly537Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000708 in 1,553,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G537R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000074 (0 hom.)
• Consequence: BEGAIN NM_001385089.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.89
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07799569).

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.1610G>C	p.Gly537Ala	missense	Exon 7 of 7	NP_001372018.1	G3V3A2
	BEGAIN	NM_001385085.1		c.1700G>C	p.Gly567Ala	missense	Exon 8 of 8	NP_001372014.1
	BEGAIN	NM_001385086.1		c.1682G>C	p.Gly561Ala	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.1610G>C	p.Gly537Ala	missense	Exon 7 of 7	ENSP00000451125.2	G3V3A2
	BEGAIN	ENST00000355173.7	TSL:1	c.1553G>C	p.Gly518Ala	missense	Exon 7 of 7	ENSP00000347301.2	Q9BUH8
	BEGAIN	ENST00000557378.6	TSL:1	c.1553G>C	p.Gly518Ala	missense	Exon 6 of 6	ENSP00000450722.2	Q9BUH8

Frequencies

GnomAD3 genomes AF: 0.0000395 AC: 6 AN: 152078 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000119 AC: 19 AN: 159606 AF XY: 0.000112

Gnomad AFR exome AF: 0.000325

Gnomad AMR exome AF: 0.000265

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000152

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000452

Gnomad OTH exome AF: 0.000472

GnomAD4 exome AF: 0.0000742 AC: 104 AN: 1400930 Hom.: 0 Cov.: 31 AF XY: 0.0000736 AC XY: 51 AN XY: 693238

African (AFR) AF: 0.000126 AC: 4 AN: 31672

American (AMR) AF: 0.000187 AC: 7 AN: 37532

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23934

East Asian (EAS) AF: 0.000160 AC: 6 AN: 37528

South Asian (SAS) AF: 0.000125 AC: 10 AN: 79920

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40752

Middle Eastern (MID) AF: 0.00461 AC: 25 AN: 5422

European-Non Finnish (NFE) AF: 0.0000396 AC: 43 AN: 1086184

Other (OTH) AF: 0.000155 AC: 9 AN: 57986

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152196 Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5 AN XY: 74394

African (AFR) AF: 0.0000481 AC: 2 AN: 41548

American (AMR) AF: 0.0000653 AC: 1 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5134

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67976

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.0000364 Hom.: 0

Bravo AF: 0.0000869

ExAC AF: 0.0000254 AC: 3

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.072
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	5.0
DANN	Benign	0.61
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.46
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.62	T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.9
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.093
Sift	Benign	1.0	T
Sift4G	Benign	0.68	T
Polyphen		0.0040	B
Vest4		0.080
MVP		0.24
MPC		0.47
ClinPred		0.011	T
GERP RS		3.3
Varity_R		0.039
gMVP		0.059
Mutation Taster		=95/5	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: rs780718553; hg19: chr14-101004535;