Variant 2-240887104-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001085437.3(MAB21L4):c.1310A>G(p.Gln437Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000349 in 1,614,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00036 ( 0 hom. )

Consequence

MAB21L4
NM_001085437.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.79

Variant links:

Genes affected

MAB21L4 (HGNC:26216): (mab-21 like 4)

MAB21L4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03005889).

BP6

Variant 2-240887104-T-C is Benign according to our data. Variant chr2-240887104-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3121832.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAB21L4	NM_001085437.3 linkuse as main transcript	c.1310A>G	p.Gln437Arg	missense_variant	5/5	ENST00000388934.5	NP_001078906.3
MAB21L4	NM_001282921.2 linkuse as main transcript	c.863A>G	p.Gln288Arg	missense_variant	5/5		NP_001269850.2
MAB21L4	NM_024861.4 linkuse as main transcript	c.806A>G	p.Gln269Arg	missense_variant	5/5		NP_079137.4
MAB21L4	XM_011511877.2 linkuse as main transcript	c.1310A>G	p.Gln437Arg	missense_variant	6/6		XP_011510179.1	Q08AI8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MAB21L4	ENST00000388934.5 linkuse as main transcript	c.1310A>G	p.Gln437Arg	missense_variant	5/5	2	NM_001085437.3	ENSP00000373586.4	Q08AI8-1
MAB21L4	ENST00000307486.12 linkuse as main transcript	c.863A>G	p.Gln288Arg	missense_variant	5/5	1		ENSP00000302779.8	Q08AI8-2
MAB21L4	ENST00000402775.6 linkuse as main transcript	c.806A>G	p.Gln269Arg	missense_variant	5/5	2		ENSP00000385338.2	Q08AI8-3

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000250

AC:

AN:

248194

Hom.:

AF XY:

0.000267

AC XY:

AN XY:

134766

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000518

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000358

AC:

524

AN:

1461838

Hom.:

Cov.:

AF XY:

0.000381

AC XY:

277

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000243

Gnomad4 NFE exome

AF:

0.000443

Gnomad4 OTH exome

AF:

0.000248

GnomAD4 genome

AF:

0.000263

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000464

Hom.:

Bravo

AF:

0.000246

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000601

AC:

ExAC

AF:

0.000248

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000415

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.10

DANN

Benign

0.26

DEOGEN2

Benign

0.0047

.;.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0049

LIST_S2

Benign

0.44

T;T;T

M_CAP

Benign

0.0018

MetaRNN

Benign

0.030

T;T;T

MetaSVM

Benign

-1.0

PROVEAN

Benign

-0.40

N;N;N

REVEL

Benign

0.018

Sift

Benign

0.97

T;T;T

Sift4G

Benign

0.74

T;T;T

Polyphen

0.0

B;.;B

Vest4

0.019

MVP

0.030

MPC

0.075

ClinPred

0.068

GERP RS

-9.1

Varity_R

0.060

gMVP

0.14

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over