16-14140643-G-A

Variant names:

• chr16-14140643-G-A
• NM_001308142.2:c.37G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001308142.2(MRTFB):​c.37G>A​(p.Val13Met) 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. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MRTFB NM_001308142.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.576
• 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_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03242764).

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.37G>A	p.Val13Met	missense	Exon 3 of 17	NP_001295071.1	Q9ULH7-5
	MRTFB	NM_001365412.2		c.37G>A	p.Val13Met	missense	Exon 4 of 17	NP_001352341.1
	MRTFB	NM_014048.4		c.37G>A	p.Val13Met	missense	Exon 3 of 17	NP_054767.3	Q9ULH7-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRTFB	ENST00000571589.6	TSL:2 MANE Select	c.37G>A	p.Val13Met	missense	Exon 3 of 17	ENSP00000459626.2	Q9ULH7-5
	MRTFB	ENST00000574045.5	TSL:1	c.37G>A	p.Val13Met	missense	Exon 3 of 17	ENSP00000459205.1	Q9ULH7-4
	MRTFB	ENST00000910537.1		c.37G>A	p.Val13Met	missense	Exon 3 of 17	ENSP00000580596.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	0.069
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	3.6
DANN	Benign	0.84
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-0.93	T
PhyloP100		-0.58
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.10	N
REVEL	Benign	0.046
Sift	Benign	0.10	T
Sift4G	Benign	0.098	T
Polyphen		0.19	B
Vest4		0.21
MutPred		0.20		Gain of helix (P = 0.1736)
MVP		0.12
MPC		0.055
ClinPred		0.083	T
GERP RS		-10
PromoterAI		-0.0024	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.095

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: chr16-14234500;