Genetic Variant ENSG00000288663:n.737C>T (chr12-53299619-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000676527.1(ENSG00000288663):n.737C>T 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 0.00000895 in 893,774 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000067 ( 0 hom. )

Consequence

ENSG00000288663
ENST00000676527.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.16

Publications

15 publications found

Variant links:

Genes affected

ENSG00000288663 (HGNC:):

ENSG00000288663 links:

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

MYG1-AS1 links:

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 links:

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]

PFDN5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
MYG1	NM_021640.4 link	c.-119C>T	upstream_gene_variant	ENST00000267103.10	NP_067653.4	Q9HB07
PFDN5	NM_002624.4 link	c.*274C>T	downstream_gene_variant	ENST00000334478.9	NP_002615.2	Q99471-1
PFDN5	NM_145897.3 link	c.*274C>T	downstream_gene_variant		NP_665904.1	Q99471-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYG1	ENST00000267103.10 link	c.-119C>T		upstream_gene_variant		1	NM_021640.4	ENSP00000267103.5		Q9HB07
PFDN5	ENST00000334478.9 link	c.*274C>T		downstream_gene_variant		1	NM_002624.4	ENSP00000334188.4		Q99471-1

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151878

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000674

AC:

AN:

741896

Hom.:

Cov.:

AF XY:

0.00000791

AC XY:

AN XY:

379198

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

19030

American (AMR)

AF:

0.00

AC:

AN:

27158

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17004

East Asian (EAS)

AF:

0.00

AC:

AN:

32556

South Asian (SAS)

AF:

0.0000354

AC:

AN:

56456

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32656

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2596

European-Non Finnish (NFE)

AF:

0.00000579

AC:

AN:

518454

Other (OTH)

AF:

0.00

AC:

AN:

35986

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151878

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74166

show subpopulations

African (AFR)

AF:

0.0000484

AC:

AN:

41336

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3450

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10570

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67958

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

606

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.4

(source)

DANN

Benign

0.92

PhyloP100

-1.2

PromoterAI

-0.034

Neutral

(source)

Splicing

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

Publications

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12-53299619-C-T

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