chr16-14240269-C-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. 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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRTFB	NM_001308142.2	c.864C>G	p.His288Gln	missense_variant	Exon 10 of 17	ENST00000571589.6	NP_001295071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRTFB	ENST00000571589.6	c.864C>G	p.His288Gln	missense_variant	Exon 10 of 17	2	NM_001308142.2	ENSP00000459626.2

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 v4.3

Name	Calibrated prediction	Score	Prediction
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;.;D;D;D
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.14	T;T;T;T;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;T;T;T;.
Polyphen		1.0, 0.95	.;D;D;.;P
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;