Variant 19-48714448-G-C 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.641C>G(p.Pro214Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000058 in 1,206,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000058 ( 0 hom. )

Consequence

MAMSTR
NM_001130915.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.148

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 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=0.05305633).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAMSTR	NM_001130915.2 linkuse as main transcript	c.641C>G	p.Pro214Arg	missense_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.641C>G	p.Pro214Arg	missense_variant	7/10	2	NM_001130915.2	ENSP00000324175.5	Q6ZN01-1
MAMSTR	ENST00000594582.1 linkuse as main transcript	c.219+358C>G		intron_variant		1		ENSP00000471590.1	Q6ZN01-3
MAMSTR	ENST00000356751.8 linkuse as main transcript	c.332C>G	p.Pro111Arg	missense_variant	5/8	2		ENSP00000349192.3	Q6ZN01-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.000111

AC:

AN:

8990

Hom.:

AF XY:

0.000191

AC XY:

AN XY:

5236

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000992

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000580

AC:

AN:

1206242

Hom.:

Cov.:

AF XY:

0.00000683

AC XY:

AN XY:

585608

show subpopulations

Gnomad4 AFR exome

AF:

0.0000414

Gnomad4 AMR exome

AF:

0.0000941

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:

0.00000400

Gnomad4 OTH exome

AF:

0.0000202

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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

Apr 19, 2023

The c.641C>G (p.P214R) alteration is located in exon 7 (coding exon 6) of the MAMSTR gene. This alteration results from a C to G substitution at nucleotide position 641, causing the proline (P) at amino acid position 214 to be replaced by an arginine (R). 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

0.14

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.18

T;.

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.60

T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.053

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;.

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-4.3

D;D

REVEL

Benign

0.026

Sift

Benign

0.13

T;T

Sift4G

Benign

0.075

T;T

Polyphen

0.073

B;.

Vest4

0.24

MutPred

0.22

Gain of MoRF binding (P = 0.0073);.;

MVP

0.22

MPC

0.92

ClinPred

0.16

GERP RS

1.7

Varity_R

0.098

gMVP

0.20

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