16-14217252-T-C

Variant names:

• chr16-14217252-T-C
• NM_001308142.2:c.479T>C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001308142.2(MRTFB):​c.479T>C​(p.Leu160Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 11/18 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MRTFB NM_001308142.2 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 7.97

Genes affected

MRTFB (HGNC:29819): (myocardin related transcription factor B) Enables transcription coactivator activity. Involved in positive regulation of pri-miRNA transcription by RNA polymerase II and positive regulation of striated muscle tissue development. Predicted to be located in cytoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.975

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRTFB	NM_001308142.2	c.479T>C	p.Leu160Pro	missense_variant	Exon 7 of 17	ENST00000571589.6	NP_001295071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRTFB	ENST00000571589.6	c.479T>C	p.Leu160Pro	missense_variant	Exon 7 of 17	2	NM_001308142.2	ENSP00000459626.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

MRTFB-related disorder Uncertain:1

Sep 24, 2024

PreventionGenetics, part of Exact Sciences

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

The MRTFB c.479T>C variant is predicted to result in the amino acid substitution p.Leu160Pro. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.58	D
BayesDel_noAF	Pathogenic	0.59
CADD	Pathogenic	30
DANN	Pathogenic	1.0
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.88
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D;.;D;D;D
M_CAP	Pathogenic	0.94	D
MetaRNN	Pathogenic	0.98	D;D;D;D;D
MetaSVM	Pathogenic	0.95	D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-6.5	.;.;D;.;.
REVEL	Pathogenic	0.97
Sift	Uncertain	0.0010	.;.;D;.;.
Sift4G	Pathogenic	0.0010	D;D;D;D;.
Polyphen		1.0	.;D;D;.;D
Vest4		0.93
MutPred		0.81		.;.;.;Gain of disorder (P = 0.0062);.;
MVP		0.97
MPC		3.4
ClinPred		1.0	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.95

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-14311109;