Variant chr19-48714367-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001130915.2(MAMSTR):c.722C>T(p.Ser241Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000227 in 1,362,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

MAMSTR
NM_001130915.2 missense, splice_region

Scores

Splicing: ADA: 0.003031

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.40

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.112475246).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAMSTR	NM_001130915.2 linkuse as main transcript	c.722C>T	p.Ser241Leu	missense_variant, splice_region_variant	7/10	ENST00000318083.11	NP_001124387.1	Q6ZN01-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MAMSTR	ENST00000318083.11 linkuse as main transcript	c.722C>T	p.Ser241Leu	missense_variant, splice_region_variant	7/10	2	NM_001130915.2	ENSP00000324175.5	Q6ZN01-1
MAMSTR	ENST00000594582.1 linkuse as main transcript	c.220-322C>T		intron_variant		1		ENSP00000471590.1	Q6ZN01-3
MAMSTR	ENST00000356751.8 linkuse as main transcript	c.413C>T	p.Ser138Leu	missense_variant, splice_region_variant	5/8	2		ENSP00000349192.3	Q6ZN01-2

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000215

AC:

AN:

1210840

Hom.:

Cov.:

AF XY:

0.0000221

AC XY:

AN XY:

587464

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000872

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000200

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000230

Gnomad4 OTH exome

AF:

0.0000201

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152110

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000378

ExAC

AF:

0.0000225

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

Jul 25, 2023

The c.722C>T (p.S241L) alteration is located in exon 7 (coding exon 6) of the MAMSTR gene. This alteration results from a C to T substitution at nucleotide position 722, causing the serine (S) at amino acid position 241 to be replaced by a leucine (L). 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

0.083

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.017

T;.

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.52

T;T

M_CAP

Benign

0.032

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;.

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.063

Sift

Benign

0.063

T;T

Sift4G

Uncertain

0.045

D;T

Polyphen

0.0010

B;.

Vest4

0.10

MutPred

0.30

Loss of phosphorylation at S241 (P = 0.006);.;

MVP

0.20

MPC

0.42

ClinPred

0.13

GERP RS

3.0

Varity_R

0.051

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0030

dbscSNV1_RF

Benign

0.25

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