Variant 19-48714898-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001130915.2(MAMSTR):c.436T>C(p.Ser146Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000168 in 1,603,806 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00016 ( 1 hom. )

Consequence

MAMSTR
NM_001130915.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0310

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.01909247).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAMSTR	NM_001130915.2 linkuse as main transcript	c.436T>C	p.Ser146Pro	missense_variant	6/10	ENST00000318083.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAMSTR	ENST00000318083.11 linkuse as main transcript	c.436T>C	p.Ser146Pro	missense_variant	6/10	2	NM_001130915.2	P2	Q6ZN01-1
MAMSTR	ENST00000594582.1 linkuse as main transcript	c.127T>C	p.Ser43Pro	missense_variant	4/7	1			Q6ZN01-3
MAMSTR	ENST00000356751.8 linkuse as main transcript	c.127T>C	p.Ser43Pro	missense_variant	4/8	2		A2	Q6ZN01-2
MAMSTR	ENST00000599703.1 linkuse as main transcript	c.586T>C	p.Ser196Pro	missense_variant	6/6	5

Frequencies

GnomAD3 genomes

AF:

0.000264

AC:

AN:

151476

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000486

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000471

Gnomad OTH

AF:

0.000481

GnomAD3 exomes

AF:

0.000232

AC:

AN:

245958

Hom.:

AF XY:

0.000301

AC XY:

AN XY:

132908

show subpopulations

Gnomad AFR exome

AF:

0.0000619

Gnomad AMR exome

AF:

0.0000294

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000665

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000434

Gnomad OTH exome

AF:

0.000837

GnomAD4 exome

AF:

0.000158

AC:

229

AN:

1452212

Hom.:

Cov.:

AF XY:

0.000172

AC XY:

124

AN XY:

722590

show subpopulations

Gnomad4 AFR exome

AF:

0.0000601

Gnomad4 AMR exome

AF:

0.0000226

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000933

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000175

Gnomad4 OTH exome

AF:

0.000167

GnomAD4 genome

AF:

0.000264

AC:

AN:

151594

Hom.:

Cov.:

AF XY:

0.000230

AC XY:

AN XY:

74010

show subpopulations

Gnomad4 AFR

AF:

0.0000485

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000209

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000471

Gnomad4 OTH

AF:

0.000476

Alfa

AF:

0.000199

Hom.:

Bravo

AF:

0.000219

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000280

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 30, 2021

The c.436T>C (p.S146P) alteration is located in exon 6 (coding exon 5) of the MAMSTR gene. This alteration results from a T to C substitution at nucleotide position 436, causing the serine (S) at amino acid position 146 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.62

Cadd

Benign

Dann

Benign

0.83

DEOGEN2

Benign

0.053

T;.;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.38

T;T;T;T

M_CAP

Benign

0.0017

MetaRNN

Benign

0.019

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;.;.;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.8

N;N;.;.

REVEL

Benign

0.039

Sift

Benign

0.090

T;T;.;.

Sift4G

Benign

0.47

T;T;T;.

Polyphen

0.0

B;.;.;.

Vest4

0.18

MVP

0.12

MPC

0.43

ClinPred

0.011

GERP RS

0.032

Varity_R

0.13

gMVP

0.23

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