NM_001130915.2:c.722C>T

Variant names:

• chr19-48714367-G-A
• rs752106987
• NM_001130915.2:c.722C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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. 16/23 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
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.112475246).

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.722C>T	p.Ser241Leu	missense splice_region	Exon 7 of 10	NP_001124387.1	Q6ZN01-1
	MAMSTR	NM_182574.3		c.413C>T	p.Ser138Leu	missense splice_region	Exon 5 of 8	NP_872380.1	Q6ZN01-2
	MAMSTR	NM_001297753.2		c.220-322C>T		intron	N/A	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.722C>T	p.Ser241Leu	missense splice_region	Exon 7 of 10	ENSP00000324175.5	Q6ZN01-1
	MAMSTR	ENST00000594582.1	TSL:1	c.220-322C>T		intron	N/A	ENSP00000471590.1	Q6ZN01-3
	MAMSTR	ENST00000599703.2	TSL:5	c.872C>T	p.Ser291Leu	missense splice_region	Exon 7 of 10	ENSP00000469544.2	M0QY28

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152110 Hom.: 0 Cov.: 31

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

GnomAD2 exomes AF: 0.000101 AC: 1 AN: 9928 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.0000215 AC: 26 AN: 1210840 Hom.: 0 Cov.: 34 AF XY: 0.0000221 AC XY: 13 AN XY: 587464

African (AFR) AF: 0.00 AC: 0 AN: 23854

American (AMR) AF: 0.0000872 AC: 1 AN: 11468

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16782

East Asian (EAS) AF: 0.00 AC: 0 AN: 27820

South Asian (SAS) AF: 0.0000200 AC: 1 AN: 50064

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28204

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4786

European-Non Finnish (NFE) AF: 0.0000230 AC: 23 AN: 998064

Other (OTH) AF: 0.0000201 AC: 1 AN: 49798

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152110 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74310

African (AFR) AF: 0.00 AC: 0 AN: 41422

American (AMR) AF: 0.000131 AC: 2 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

ExAC AF: 0.0000225 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		1.4
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.063
Sift	Benign	0.063	T
Sift4G	Uncertain	0.045	D
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	T
GERP RS		3.0
Varity_R		0.051
gMVP		0.14
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs752106987; hg19: chr19-49217624; COSMIC: COSV58882339; COSMIC: COSV58882339;