chr12-53299748-A-G

Position:

• chr12-53299748-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021640.4(MYG1):​c.11A>G​(p.Gln4Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.99 in 1,613,020 control chromosomes in the GnomAD database, including 792,181 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.95 (68974 hom., cov: 31)
  • Exomes 𝑓: 0.99 (723207 hom.)
• Consequence: MYG1 NM_021640.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.650

Genes affected

MYG1 (HGNC:17590): (MYG1 exonuclease) Predicted to enable nuclease activity. Predicted to be involved in nucleic acid phosphodiester bond hydrolysis. Predicted to act upstream of or within locomotory exploration behavior. Located in mitochondrion and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MYG1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.2240062E-6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYG1	NM_021640.4	c.11A>G	p.Gln4Arg	missense_variant	1/7	ENST00000267103.10	NP_067653.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYG1	ENST00000267103.10	c.11A>G	p.Gln4Arg	missense_variant	1/7	1	NM_021640.4	ENSP00000267103.5

Frequencies

GnomAD3 genomes AF: 0.950 AC: 144210 AN: 151870 Hom.: 68936 Cov.: 31

Gnomad AFR AF: 0.823

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.984

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.998

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.990

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.971

GnomAD3 exomes AF: 0.987 AC: 243978 AN: 247154 Hom.: 120642 AF XY: 0.991 AC XY: 133069 AN XY: 134316

Gnomad AFR exome AF: 0.817

Gnomad AMR exome AF: 0.993

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.995

GnomAD4 exome AF: 0.995 AC: 1453088 AN: 1461032 Hom.: 723207 Cov.: 58 AF XY: 0.995 AC XY: 723443 AN XY: 726826

Gnomad4 AFR exome AF: 0.806

Gnomad4 AMR exome AF: 0.991

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.988

GnomAD4 genome AF: 0.949 AC: 144304 AN: 151988 Hom.: 68974 Cov.: 31 AF XY: 0.951 AC XY: 70663 AN XY: 74320

Gnomad4 AFR AF: 0.822

Gnomad4 AMR AF: 0.984

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 0.971

Alfa AF: 0.991 Hom.: 113640

Bravo AF: 0.942

TwinsUK AF: 1.00 AC: 3707

ALSPAC AF: 0.999 AC: 3852

ESP6500AA AF: 0.824 AC: 3632

ESP6500EA AF: 1.00 AC: 8592

ExAC AF: 0.983 AC: 119221

Asia WGS AF: 0.988 AC: 3435 AN: 3478

EpiCase AF: 1.00

EpiControl AF: 0.999

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.9
DANN	Benign	0.33
DEOGEN2	Benign	0.053	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.00052	N
LIST_S2	Benign	0.18	T
MetaRNN	Benign	0.0000012	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.90	N
PROVEAN	Benign	0.38	N
REVEL	Benign	0.032
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.010
MPC		0.16
ClinPred		0.0032	T
GERP RS		-0.12
Varity_R		0.032
gMVP		0.31

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

LitVar

Other links and lift over

dbSNP: rs1534284; hg19: chr12-53693532;