chr18-3253944-C-T

Variant names:

• chr18-3253944-C-T
• rs61751192
• NM_006471.4:c.237C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_006471.4(MYL12A):​c.237C>T​(p.Pro79Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00229 in 1,613,868 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (40 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (47 hom.)
• Consequence: MYL12A NM_006471.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.205
• Publications: 3 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: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 18-3253944-C-T is Benign according to our data. Variant chr18-3253944-C-T is described in ClinVar as Benign. ClinVar VariationId is 768927.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.205 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0119 (1817/152162) while in subpopulation AFR AF = 0.0418 (1736/41506). AF 95% confidence interval is 0.0402. There are 40 homozygotes in GnomAd4. There are 858 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1817 AD gene.

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>T	p.Pro79Pro	synonymous	Exon 3 of 4	NP_006462.1	P19105
	MYL12A	NM_001303049.2		c.255C>T	p.Pro85Pro	synonymous	Exon 3 of 4	NP_001289978.1	J3QRS3
	MYL12A	NM_001303047.2		c.237C>T	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>T	p.Pro79Pro	synonymous	Exon 3 of 4	ENSP00000217652.3	P19105
	MYL12A	ENST00000580887.5	TSL:1	c.255C>T	p.Pro85Pro	synonymous	Exon 3 of 4	ENSP00000464359.1	J3QRS3
	MYL12A	ENST00000536605.1	TSL:1	c.237C>T	p.Pro79Pro	synonymous	Exon 3 of 4	ENSP00000441231.1	P19105

Frequencies

GnomAD3 genomes AF: 0.0119 AC: 1810 AN: 152044 Hom.: 39 Cov.: 32

Gnomad AFR AF: 0.0418

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00400

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.00289 AC: 727 AN: 251278 AF XY: 0.00203

Gnomad AFR exome AF: 0.0401

Gnomad AMR exome AF: 0.00148

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000114

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.00129 AC: 1882 AN: 1461706 Hom.: 47 Cov.: 31 AF XY: 0.00110 AC XY: 801 AN XY: 727144

African (AFR) AF: 0.0457 AC: 1529 AN: 33458

American (AMR) AF: 0.00177 AC: 79 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00208 AC: 12 AN: 5764

European-Non Finnish (NFE) AF: 0.0000648 AC: 72 AN: 1111914

Other (OTH) AF: 0.00298 AC: 180 AN: 60388

GnomAD4 genome AF: 0.0119 AC: 1817 AN: 152162 Hom.: 40 Cov.: 32 AF XY: 0.0115 AC XY: 858 AN XY: 74390

African (AFR) AF: 0.0418 AC: 1736 AN: 41506

American (AMR) AF: 0.00392 AC: 60 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68004

Other (OTH) AF: 0.00615 AC: 13 AN: 2114

Alfa AF: 0.00366 Hom.: 1

Bravo AF: 0.0134

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	13
DANN	Benign	0.69
PhyloP100		0.20
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs61751192; hg19: chr18-3253942;