chr11-60337907-C-T

Position:

chr11-60337907-C-T

Variant summary

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

The NM_139249.4(MS4A6E):c.314C>T(p.Pro105Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,614,070 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

MS4A6E
NM_139249.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00500

Variant links:

Genes affected

MS4A6E (HGNC:14285): (membrane spanning 4-domains A6E) This gene encodes a member of the membrane-spanning 4A gene family. Members of this nascent protein family are characterized by common structural features and similar intron/exon splice boundaries and display unique expression patterns among hematopoietic cells and nonlymphoid tissues. The gene encoding this protein is localized to 11q12.3, among a cluster of family members. [provided by RefSeq, Jul 2008]

MS4A6E 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=0.042898268).

BP6

Variant 11-60337907-C-T is Benign according to our data. Variant chr11-60337907-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2477870.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MS4A6E	NM_139249.4 linkuse as main transcript	c.314C>T	p.Pro105Leu	missense_variant	3/5	ENST00000684409.1
MS4A6E	NR_170614.1 linkuse as main transcript	n.482C>T		non_coding_transcript_exon_variant	3/6
MS4A6E	NR_170616.1 linkuse as main transcript	n.602C>T		non_coding_transcript_exon_variant	4/6
MS4A6E	NR_170615.1 linkuse as main transcript	n.541+61C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MS4A6E	ENST00000684409.1 linkuse as main transcript	c.314C>T	p.Pro105Leu	missense_variant	3/5		NM_139249.4	P1
MS4A6E	ENST00000300182.8 linkuse as main transcript	c.314C>T	p.Pro105Leu	missense_variant	2/4	1		P1
MS4A6E	ENST00000532756.1 linkuse as main transcript	c.239C>T	p.Pro80Leu	missense_variant, NMD_transcript_variant	2/5	4
MS4A6E	ENST00000530509.1 linkuse as main transcript	c.*112+61C>T		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251304

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135798

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:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000171

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Jan 23, 2023

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

0.085

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.032

DANN

Benign

0.20

DEOGEN2

Benign

0.0011

Eigen

Benign

-2.3

Eigen_PC

Benign

-2.4

FATHMM_MKL

Benign

0.0021

LIST_S2

Benign

0.30

M_CAP

Benign

0.0020

MetaRNN

Benign

0.043

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.63

MutationTaster

Benign

1.0

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.80

REVEL

Benign

0.011

Sift

Benign

0.70

Sift4G

Benign

0.72

Polyphen

0.0060

Vest4

0.063

MutPred

0.49

Loss of loop (P = 0.0073);

MVP

0.043

MPC

0.033

ClinPred

0.026

GERP RS

-3.8

Varity_R

0.020

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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