Genetic Variant MAMSTR:p.Gly388Arg (chr19-48713353-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001130915.2(MAMSTR):c.1162G>C(p.Gly388Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,455,820 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G388C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MAMSTR
NM_001130915.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.73

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: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2679184).

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.1162G>C	p.Gly388Arg	missense	Exon 10 of 10	NP_001124387.1	Q6ZN01-1
MAMSTR	NM_182574.3		c.853G>C	p.Gly285Arg	missense	Exon 8 of 8	NP_872380.1	Q6ZN01-2
MAMSTR	NM_001297753.2		c.658G>C	p.Gly220Arg	missense	Exon 7 of 7	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.1162G>C	p.Gly388Arg	missense	Exon 10 of 10	ENSP00000324175.5	Q6ZN01-1
MAMSTR	ENST00000594582.1	TSL:1	c.658G>C	p.Gly220Arg	missense	Exon 7 of 7	ENSP00000471590.1	Q6ZN01-3
MAMSTR	ENST00000599703.2	TSL:5	c.1312G>C	p.Gly438Arg	missense	Exon 10 of 10	ENSP00000469544.2	M0QY28

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1455820

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724636

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33046

American (AMR)

AF:

0.00

AC:

AN:

42158

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25748

East Asian (EAS)

AF:

0.00

AC:

AN:

39668

South Asian (SAS)

AF:

0.00

AC:

AN:

85970

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53024

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5668

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1110396

Other (OTH)

AF:

0.00

AC:

AN:

60142

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Benign

-0.017

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.063

Eigen

Benign

0.18

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.85

M_CAP

Benign

0.019

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.81

PhyloP100

1.7

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-2.3

REVEL

Benign

0.096

Sift

Uncertain

0.0010

Sift4G

Benign

0.14

Polyphen

0.98

Vest4

0.49

MutPred

0.13

Loss of relative solvent accessibility (P = 0.0404)

MVP

0.30

MPC

0.34

ClinPred

0.61

GERP RS

1.9

Varity_R

0.18

gMVP

0.076

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over