18-3253251-TC-CT

Variant names:

• chr18-3253251-TC-CT
• NM_006471.4:c.4_5delTCinsCT
• MYL12A p.Ser2Leu

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_006471.4(MYL12A):​c.4_5delTCinsCT​(p.Ser2Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S2W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYL12A NM_006471.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.4_5delTCinsCT	p.Ser2Leu	missense	N/A	NP_006462.1	P19105
	MYL12A	NM_001303049.2		c.22_23delTCinsCT	p.Ser8Leu	missense	N/A	NP_001289978.1	J3QRS3
	MYL12A	NM_001303047.2		c.4_5delTCinsCT	p.Ser2Leu	missense	N/A	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.4_5delTCinsCT	p.Ser2Leu	missense	N/A	ENSP00000217652.3	P19105
	MYL12A	ENST00000580887.5	TSL:1	c.22_23delTCinsCT	p.Ser8Leu	missense	N/A	ENSP00000464359.1	J3QRS3
	MYL12A	ENST00000536605.1	TSL:1	c.4_5delTCinsCT	p.Ser2Leu	missense	N/A	ENSP00000441231.1	P19105

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.9

Splicing

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: chr18-3253249;