18-3253944-C-A

Variant names:

• chr18-3253944-C-A
• NM_006471.4:c.237C>A
• MYL12A p.Pro79Pro

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_006471.4(MYL12A):​c.237C>A​(p.Pro79Pro) variant causes a synonymous 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. Synonymous variant affecting the same amino acid position (i.e. P79P) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYL12A NM_006471.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.205
• Publications: 0 publications found

Genes affected

MYL12A (HGNC:16701): (myosin light chain 12A) This gene encodes a nonsarcomeric myosin regulatory light chain. This protein is activated by phosphorylation and regulates smooth muscle and non-muscle cell contraction. This protein may also be involved in DNA damage repair by sequestering the transcriptional regulator apoptosis-antagonizing transcription factor (AATF)/Che-1 which functions as a repressor of p53-driven apoptosis. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 8.[provided by RefSeq, Dec 2014]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP7: Synonymous conserved (PhyloP=0.205 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006471.4. 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
	MYL12A	NM_006471.4	MANE Select	c.237C>A	p.Pro79Pro	synonymous	Exon 3 of 4	NP_006462.1	P19105
	MYL12A	NM_001303049.2		c.255C>A	p.Pro85Pro	synonymous	Exon 3 of 4	NP_001289978.1	J3QRS3
	MYL12A	NM_001303047.2		c.237C>A	p.Pro79Pro	synonymous	Exon 4 of 5	NP_001289976.1	P19105

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYL12A	ENST00000217652.8	TSL:1 MANE Select	c.237C>A	p.Pro79Pro	synonymous	Exon 3 of 4	ENSP00000217652.3	P19105
	MYL12A	ENST00000580887.5	TSL:1	c.255C>A	p.Pro85Pro	synonymous	Exon 3 of 4	ENSP00000464359.1	J3QRS3
	MYL12A	ENST00000536605.1	TSL:1	c.237C>A	p.Pro79Pro	synonymous	Exon 3 of 4	ENSP00000441231.1	P19105

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	12
DANN	Benign	0.77
PhyloP100		0.20

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr18-3253942;