18-3256114-A-G

Variant names:

• chr18-3256114-A-G
• rs7811
• NM_006471.4:c.*196A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006471.4(MYL12A):​c.*196A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 685,152 control chromosomes in the GnomAD database, including 8,188 homozygotes. 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: 𝑓 0.15 (1812 hom., cov: 33)
  • Exomes 𝑓: 0.15 (6376 hom.)
• Consequence: MYL12A NM_006471.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.877
• Publications: 21 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]

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

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.*196A>G		3_prime_UTR	Exon 4 of 4	NP_006462.1	P19105
	MYL12A	NM_001303049.2		c.*196A>G		3_prime_UTR	Exon 4 of 4	NP_001289978.1	J3QRS3
	MYL12A	NM_001303047.2		c.*196A>G		3_prime_UTR	Exon 5 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.*196A>G		3_prime_UTR	Exon 4 of 4	ENSP00000217652.3	P19105
	MYL12A	ENST00000580887.5	TSL:1	c.*196A>G		3_prime_UTR	Exon 4 of 4	ENSP00000464359.1	J3QRS3
	MYL12A	ENST00000536605.1	TSL:1	c.*196A>G		3_prime_UTR	Exon 4 of 4	ENSP00000441231.1	P19105

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22775 AN: 152092 Hom.: 1805 Cov.: 33

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.0870

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.132

GnomAD4 exome AF: 0.146 AC: 77642 AN: 532942 Hom.: 6376 Cov.: 7 AF XY: 0.146 AC XY: 40508 AN XY: 277802

African (AFR) AF: 0.158 AC: 2134 AN: 13520

American (AMR) AF: 0.0772 AC: 1249 AN: 16176

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 1909 AN: 13892

East Asian (EAS) AF: 0.267 AC: 8031 AN: 30034

South Asian (SAS) AF: 0.159 AC: 7008 AN: 44136

European-Finnish (FIN) AF: 0.237 AC: 7937 AN: 33462

Middle Eastern (MID) AF: 0.0691 AC: 148 AN: 2142

European-Non Finnish (NFE) AF: 0.129 AC: 45224 AN: 351300

Other (OTH) AF: 0.142 AC: 4002 AN: 28280

GnomAD4 genome AF: 0.150 AC: 22819 AN: 152210 Hom.: 1812 Cov.: 33 AF XY: 0.155 AC XY: 11540 AN XY: 74412

African (AFR) AF: 0.167 AC: 6929 AN: 41542

American (AMR) AF: 0.0868 AC: 1328 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 459 AN: 3472

East Asian (EAS) AF: 0.259 AC: 1345 AN: 5188

South Asian (SAS) AF: 0.167 AC: 807 AN: 4822

European-Finnish (FIN) AF: 0.243 AC: 2566 AN: 10576

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8936 AN: 67992

Other (OTH) AF: 0.135 AC: 286 AN: 2114

Alfa AF: 0.132 Hom.: 5384

Bravo AF: 0.138

Asia WGS AF: 0.221 AC: 769 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	12
DANN	Benign	0.68
PhyloP100		0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs7811; hg19: chr18-3256112;