Genetic Variant BEGAIN:p.Pro414Leu (chr14-100538567-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001385089.1(BEGAIN):c.1241C>T(p.Pro414Leu) 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. 12/21 in silico tools predict 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. P414Q) 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.08

Publications

0 publications found

Variant links:

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 links:

LOC124903382 (HGNC:):

LOC124903382 links:

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ACMG classification

Classification was made for transcript

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=0.22764993).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BEGAIN	NM_001385089.1	MANE Select	c.1241C>T	p.Pro414Leu	missense	Exon 7 of 7	NP_001372018.1	G3V3A2
BEGAIN	NM_001385085.1		c.1331C>T	p.Pro444Leu	missense	Exon 8 of 8	NP_001372014.1
BEGAIN	NM_001385086.1		c.1313C>T	p.Pro438Leu	missense	Exon 8 of 8	NP_001372015.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BEGAIN	ENST00000554140.3	TSL:5 MANE Select	c.1241C>T	p.Pro414Leu	missense	Exon 7 of 7	ENSP00000451125.2	G3V3A2
BEGAIN	ENST00000355173.7	TSL:1	c.1184C>T	p.Pro395Leu	missense	Exon 7 of 7	ENSP00000347301.2	Q9BUH8
BEGAIN	ENST00000557378.6	TSL:1	c.1184C>T	p.Pro395Leu	missense	Exon 6 of 6	ENSP00000450722.2	Q9BUH8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1391284

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

685236

African (AFR)

AF:

0.00

AC:

AN:

32118

American (AMR)

AF:

0.00

AC:

AN:

34754

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23346

East Asian (EAS)

AF:

0.00

AC:

AN:

37446

South Asian (SAS)

AF:

0.00

AC:

AN:

76394

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47548

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5544

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1076614

Other (OTH)

AF:

0.00

AC:

AN:

57520

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.033

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.69

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.071

MetaRNN

Benign

0.23

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

PhyloP100

2.1

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.063

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.035

Polyphen

0.76

Vest4

0.12

MutPred

0.37

Gain of catalytic residue at N396 (P = 0.0025)

MVP

0.12

MPC

1.0

ClinPred

0.63

GERP RS

2.4

Varity_R

0.23

gMVP

0.35

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over