NM_001130915.2:c.689C>T

Variant names:

• chr19-48714400-G-A
• rs745811472
• NM_001130915.2:c.689C>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.689C>T​(p.Pro230Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000647 in 1,390,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P230T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000040 (0 hom.)
• Consequence: MAMSTR NM_001130915.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.72
• 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=0.23916888).

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.689C>T	p.Pro230Leu	missense	Exon 7 of 10	NP_001124387.1	Q6ZN01-1
	MAMSTR	NM_182574.3		c.380C>T	p.Pro127Leu	missense	Exon 5 of 8	NP_872380.1	Q6ZN01-2
	MAMSTR	NM_001297753.2		c.220-355C>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.689C>T	p.Pro230Leu	missense	Exon 7 of 10	ENSP00000324175.5	Q6ZN01-1
	MAMSTR	ENST00000594582.1	TSL:1	c.220-355C>T		intron	N/A	ENSP00000471590.1	Q6ZN01-3
	MAMSTR	ENST00000599703.2	TSL:5	c.839C>T	p.Pro280Leu	missense	Exon 7 of 10	ENSP00000469544.2	M0QY28

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152116 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 19018 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: 0.00000404 AC: 5 AN: 1238336 Hom.: 0 Cov.: 34 AF XY: 0.00000661 AC XY: 4 AN XY: 604872

African (AFR) AF: 0.00 AC: 0 AN: 24108

American (AMR) AF: 0.00 AC: 0 AN: 13282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17930

East Asian (EAS) AF: 0.00 AC: 0 AN: 28064

South Asian (SAS) AF: 0.0000179 AC: 1 AN: 55770

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4840

European-Non Finnish (NFE) AF: 0.00000395 AC: 4 AN: 1013912

Other (OTH) AF: 0.00 AC: 0 AN: 51078

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152116 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74326

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15280

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000240 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	0.23
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.10
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.080	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.7	L
PhyloP100		2.7
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.10
Sift	Uncertain	0.017	D
Sift4G	Benign	0.22	T
Polyphen		0.99	D
Vest4		0.36
MutPred		0.23		Loss of glycosylation at P230 (P = 0.0368)
MVP		0.34
MPC		0.76
ClinPred		0.98	D
GERP RS		2.9
Varity_R		0.18
gMVP		0.33
Mutation Taster		=77/23	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: rs745811472; hg19: chr19-49217657;