dbSNP rs2032889995: MAMSTR:p.Arg238Leu (chr19-48714376-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001130915.2(MAMSTR):c.713G>T(p.Arg238Leu) 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. 14/21 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. R238H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MAMSTR
NM_001130915.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.406

Publications

0 publications found

Variant links:

Genes affected

MAMSTR (HGNC:26689): (MEF2 activating motif and SAP domain containing transcriptional regulator) Predicted to enable transcription coregulator activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within positive regulation of myotube differentiation and positive regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MAMSTR links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06595883).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130915.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAMSTR	NM_001130915.2	MANE Select	c.713G>T	p.Arg238Leu	missense	Exon 7 of 10	NP_001124387.1	Q6ZN01-1
MAMSTR	NM_182574.3		c.404G>T	p.Arg135Leu	missense	Exon 5 of 8	NP_872380.1	Q6ZN01-2
MAMSTR	NM_001297753.2		c.220-331G>T		intron	N/A	NP_001284682.1	Q6ZN01-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAMSTR	ENST00000318083.11	TSL:2 MANE Select	c.713G>T	p.Arg238Leu	missense	Exon 7 of 10	ENSP00000324175.5	Q6ZN01-1
MAMSTR	ENST00000594582.1	TSL:1	c.220-331G>T		intron	N/A	ENSP00000471590.1	Q6ZN01-3
MAMSTR	ENST00000599703.2	TSL:5	c.863G>T	p.Arg288Leu	missense	Exon 7 of 10	ENSP00000469544.2	M0QY28

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1212204

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

588452

African (AFR)

AF:

0.00

AC:

AN:

23884

American (AMR)

AF:

0.00

AC:

AN:

11964

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17010

East Asian (EAS)

AF:

0.00

AC:

AN:

27742

South Asian (SAS)

AF:

0.00

AC:

AN:

50748

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28338

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4804

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

997856

Other (OTH)

AF:

0.00

AC:

AN:

49858

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.019

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.068

LIST_S2

Benign

0.66

M_CAP

Benign

0.019

MetaRNN

Benign

0.066

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.83

PhyloP100

0.41

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.97

REVEL

Benign

0.024

Sift

Benign

0.18

Sift4G

Benign

0.32

Polyphen

0.017

Vest4

0.29

MutPred

0.19

Loss of methylation at R238 (P = 0.0116)

MVP

0.12

MPC

0.36

ClinPred

0.11

GERP RS

3.0

Varity_R

0.045

gMVP

0.23

Mutation Taster

=89/11

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