NM_001308142.2:c.271G>C

Variant names:

• chr16-14212404-G-C
• NM_001308142.2:c.271G>C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Moderate PP5_Moderate

The NM_001308142.2(MRTFB):​c.271G>C​(p.Ala91Pro) 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. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MRTFB NM_001308142.2 missense
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 8.02
• Publications: 0 publications found

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]

MRTFB Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.897
• PP5: Variant 16-14212404-G-C is Pathogenic according to our data. Variant chr16-14212404-G-C is described in ClinVar as Pathogenic. ClinVar VariationId is 1723884.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308142.2. 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
	MRTFB	NM_001308142.2	MANE Select	c.271G>C	p.Ala91Pro	missense	Exon 5 of 17	NP_001295071.1	Q9ULH7-5
	MRTFB	NM_001365411.2		c.238G>C	p.Ala80Pro	missense	Exon 3 of 15	NP_001352340.1	Q9ULH7-1
	MRTFB	NM_001365412.2		c.271G>C	p.Ala91Pro	missense	Exon 6 of 17	NP_001352341.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRTFB	ENST00000571589.6	TSL:2 MANE Select	c.271G>C	p.Ala91Pro	missense	Exon 5 of 17	ENSP00000459626.2	Q9ULH7-5
	MRTFB	ENST00000574045.5	TSL:1	c.271G>C	p.Ala91Pro	missense	Exon 5 of 17	ENSP00000459205.1	Q9ULH7-4
	MRTFB	ENST00000573051.1	TSL:1	c.118G>C	p.Ala40Pro	missense	Exon 3 of 9	ENSP00000460589.1	Q9ULH7-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
2	-	-	MRTFB-related disorder (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.54	D
BayesDel_noAF	Pathogenic	0.54
CADD	Pathogenic	32
DANN	Uncertain	1.0
Eigen	Pathogenic	0.97
Eigen_PC	Pathogenic	0.95
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Pathogenic	0.80	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Pathogenic	0.92	D
PhyloP100		8.0
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-4.2	D
REVEL	Pathogenic	0.77
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.90
MutPred		0.36		Gain of glycosylation at A80 (P = 0.0411)
MVP		0.98
MPC		3.0
ClinPred		1.0	D
GERP RS		5.8
gMVP		0.83

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

hg19: chr16-14306261;