18-3255904-G-A

Variant names:

• chr18-3255904-G-A
• NM_006471.4:c.502G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006471.4(MYL12A):​c.502G>A​(p.Asp168Asn) variant causes a missense change involving the alteration of a 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.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MYL12A NM_006471.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.60

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]

MYL12-AS1 (HGNC:55331): (MYL12A and MYL12B antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36381093).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYL12A	NM_006471.4	c.502G>A	p.Asp168Asn	missense_variant	Exon 4 of 4	ENST00000217652.8	NP_006462.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYL12A	ENST00000217652.8	c.502G>A	p.Asp168Asn	missense_variant	Exon 4 of 4	1	NM_006471.4	ENSP00000217652.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.502G>A (p.D168N) alteration is located in exon 4 (coding exon 3) of the MYL12A gene. This alteration results from a G to A substitution at nucleotide position 502, causing the aspartic acid (D) at amino acid position 168 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Uncertain	0.025	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.074	T;T;T;T;T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.92	.;.;.;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.36	T;T;T;T;T
MetaSVM	Uncertain	-0.034	T
MutationAssessor	Uncertain	2.4	M;M;M;.;M
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-3.5	.;D;.;.;D
REVEL	Uncertain	0.51
Sift	Uncertain	0.0010	.;D;.;.;D
Sift4G	Uncertain	0.0030	D;D;D;D;D
Polyphen		0.92	P;P;P;.;P
Vest4		0.44
MutPred		0.35		Gain of MoRF binding (P = 0.0387);Gain of MoRF binding (P = 0.0387);Gain of MoRF binding (P = 0.0387);.;Gain of MoRF binding (P = 0.0387);
MVP		0.77
MPC		1.5
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.65
gMVP		0.51

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-3255902;