12-53299619-C-G

Variant names:

• chr12-53299619-C-G
• rs1465073
• ENST00000676527.1:n.737C>G

Variant summary

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

The ENST00000676527.1(ENSG00000288663):​n.737C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 892,408 control chromosomes in the GnomAD database, including 71,848 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 0.35 (10128 hom., cov: 32)
  • Exomes 𝑓: 0.40 (61720 hom.)
• Consequence: ENSG00000288663 ENST00000676527.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

Genes affected

ENSG00000288663 (HGNC:):

MYG1-AS1 (HGNC:54810): (MYG1 antisense RNA 1)

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]

PFDN5 (HGNC:8869): (prefoldin subunit 5) This gene encodes a member of the prefoldin alpha subunit family. The encoded protein is one of six subunits of prefoldin, a molecular chaperone complex that binds and stabilizes newly synthesized polypeptides, thereby allowing them to fold correctly. The complex, consisting of two alpha and four beta subunits, forms a double beta barrel assembly with six protruding coiled-coils. The encoded protein may also repress the transcriptional activity of the proto-oncogene c-Myc. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYG1	NM_021640.4	c.-119C>G		upstream_gene_variant		ENST00000267103.10	NP_067653.4
PFDN5	NM_002624.4	c.*274C>G		downstream_gene_variant		ENST00000334478.9	NP_002615.2
PFDN5	NM_145897.3	c.*274C>G		downstream_gene_variant			NP_665904.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYG1	ENST00000267103.10	c.-119C>G		upstream_gene_variant		1	NM_021640.4	ENSP00000267103.5
PFDN5	ENST00000334478.9	c.*274C>G		downstream_gene_variant		1	NM_002624.4	ENSP00000334188.4

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53662 AN: 151790 Hom.: 10113 Cov.: 32

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.369

GnomAD4 exome AF: 0.401 AC: 296987 AN: 740498 Hom.: 61720 Cov.: 10 AF XY: 0.407 AC XY: 154129 AN XY: 378500

Gnomad4 AFR exome AF: 0.233

Gnomad4 AMR exome AF: 0.468

Gnomad4 ASJ exome AF: 0.407

Gnomad4 EAS exome AF: 0.596

Gnomad4 SAS exome AF: 0.535

Gnomad4 FIN exome AF: 0.377

Gnomad4 NFE exome AF: 0.378

Gnomad4 OTH exome AF: 0.397

GnomAD4 genome AF: 0.354 AC: 53708 AN: 151910 Hom.: 10128 Cov.: 32 AF XY: 0.356 AC XY: 26436 AN XY: 74244

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.404

Gnomad4 EAS AF: 0.595

Gnomad4 SAS AF: 0.549

Gnomad4 FIN AF: 0.368

Gnomad4 NFE AF: 0.378

Gnomad4 OTH AF: 0.377

Alfa AF: 0.241 Hom.: 606

Bravo AF: 0.351

Asia WGS AF: 0.544 AC: 1893 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.0
DANN	Benign	0.46

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1465073; hg19: chr12-53693403;