Genetic Variant MYL12A:c.*196A>G (chr18-3256114-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.877

Publications

21 publications found

Variant links:

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]

MYL12A links:

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

MYL12-AS1 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYL12A	NM_006471.4 link	c.*196A>G		3_prime_UTR_variant	Exon 4 of 4	ENST00000217652.8	NP_006462.1	P19105

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYL12A	ENST00000217652.8 link	c.*196A>G		3_prime_UTR_variant	Exon 4 of 4	1	NM_006471.4	ENSP00000217652.3		P19105

Frequencies

GnomAD3 genomes

AF:

0.150

AC:

22775

AN:

152092

Hom.:

1805

Cov.:

show subpopulations

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.:

AF XY:

0.146

AC XY:

40508

AN XY:

277802

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

3125

6250

9376

12501

15626

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

700

1400

2100

2800

3500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.150

AC:

22819

AN:

152210

Hom.:

1812

Cov.:

AF XY:

0.155

AC XY:

11540

AN XY:

74412

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.131

AC:

8936

AN:

67992

Other (OTH)

AF:

0.135

AC:

286

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

993

1986

2979

3972

4965

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

256

512

768

1024

1280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

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)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over