NM_001308142.2:c.864C>G

Variant names:

• chr16-14240269-C-G
• rs75963814
• NM_001308142.2:c.864C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001308142.2(MRTFB):​c.864C>G​(p.His288Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MRTFB NM_001308142.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• Publications: 9 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

ENSG00000305939 (HGNC:):

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=0.13579533).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRTFB	NM_001308142.2	MANE Select	c.864C>G	p.His288Gln	missense	Exon 10 of 17	NP_001295071.1
	MRTFB	NM_001365411.2		c.831C>G	p.His277Gln	missense	Exon 8 of 15	NP_001352340.1
	MRTFB	NM_001365412.2		c.864C>G	p.His288Gln	missense	Exon 11 of 17	NP_001352341.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRTFB	ENST00000571589.6	TSL:2 MANE Select	c.864C>G	p.His288Gln	missense	Exon 10 of 17	ENSP00000459626.2
	MRTFB	ENST00000574045.5	TSL:1	c.864C>G	p.His288Gln	missense	Exon 10 of 17	ENSP00000459205.1
	MRTFB	ENST00000573051.1	TSL:1	c.711C>G	p.His237Gln	missense	Exon 8 of 9	ENSP00000460589.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 64

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	19
DANN	Uncertain	0.99
Eigen	Benign	0.013
Eigen_PC	Benign	0.092
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.87	T
PhyloP100		1.0
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	0.46	N
REVEL	Uncertain	0.30
Sift	Benign	0.75	T
Sift4G	Benign	0.88	T
Polyphen		1.0	D
Vest4		0.51
MutPred		0.070		Gain of methylation at K280 (P = 0.1087)
MVP		0.59
MPC		0.43
ClinPred		0.72	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.48

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: rs75963814; hg19: chr16-14334126;