19-48713542-G-T

Variant names:

• chr19-48713542-G-T
• rs562969140
• NM_001130915.2:c.973C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001130915.2(MAMSTR):​c.973C>A​(p.Pro325Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. P325S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MAMSTR NM_001130915.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.99
• Publications: 1 publications found

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]

ACMG classification

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=0.3041221).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAMSTR	NM_001130915.2	MANE Select	c.973C>A	p.Pro325Thr	missense	Exon 10 of 10	NP_001124387.1	Q6ZN01-1
	MAMSTR	NM_182574.3		c.664C>A	p.Pro222Thr	missense	Exon 8 of 8	NP_872380.1	Q6ZN01-2
	MAMSTR	NM_001297753.2		c.469C>A	p.Pro157Thr	missense	Exon 7 of 7	NP_001284682.1	Q6ZN01-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAMSTR	ENST00000318083.11	TSL:2 MANE Select	c.973C>A	p.Pro325Thr	missense	Exon 10 of 10	ENSP00000324175.5	Q6ZN01-1
	MAMSTR	ENST00000594582.1	TSL:1	c.469C>A	p.Pro157Thr	missense	Exon 7 of 7	ENSP00000471590.1	Q6ZN01-3
	MAMSTR	ENST00000599703.2	TSL:5	c.1123C>A	p.Pro375Thr	missense	Exon 10 of 10	ENSP00000469544.2	M0QY28

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000412 AC: 1 AN: 242970 AF XY: 0.00000754

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000298

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 6.86e-7 AC: 1 AN: 1458132 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725382

African (AFR) AF: 0.00 AC: 0 AN: 33262

American (AMR) AF: 0.0000228 AC: 1 AN: 43868

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25964

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86130

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52940

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5492

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110598

Other (OTH) AF: 0.00 AC: 0 AN: 60194

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.070	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.30	T
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Benign	0.90	L
PhyloP100		5.0
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.096
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.023	D
Polyphen		1.0	D
Vest4		0.41
MutPred		0.27		Gain of phosphorylation at P325 (P = 0.0081)
MVP		0.50
MPC		0.75
ClinPred		0.51	D
GERP RS		4.6
Varity_R		0.22
gMVP		0.26
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

dbSNP: rs562969140; hg19: chr19-49216799;