Genetic Variant ENSG00000288663:n.737C>G (chr12-53299619-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

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

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: Benign. The variant received -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	Effect	MANE	Protein	UniProt
MYG1	NM_021640.4 link	c.-119C>G	upstream_gene_variant	ENST00000267103.10	NP_067653.4	Q9HB07
PFDN5	NM_002624.4 link	c.*274C>G	downstream_gene_variant	ENST00000334478.9	NP_002615.2	Q99471-1
PFDN5	NM_145897.3 link	c.*274C>G	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>G		upstream_gene_variant		1	NM_021640.4	ENSP00000267103.5		Q9HB07
PFDN5	ENST00000334478.9 link	c.*274C>G		downstream_gene_variant		1	NM_002624.4	ENSP00000334188.4		Q99471-1

Frequencies

GnomAD3 genomes

AF:

0.354

AC:

53662

AN:

151790

Hom.:

10113

Cov.:

show subpopulations

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.:

AF XY:

0.407

AC XY:

154129

AN XY:

378500

show subpopulations

African (AFR)

AF:

0.233

AC:

4426

AN:

19008

American (AMR)

AF:

0.468

AC:

12682

AN:

27120

Ashkenazi Jewish (ASJ)

AF:

0.407

AC:

6924

AN:

16994

East Asian (EAS)

AF:

0.596

AC:

19386

AN:

32544

South Asian (SAS)

AF:

0.535

AC:

30164

AN:

56426

European-Finnish (FIN)

AF:

0.377

AC:

12322

AN:

32642

Middle Eastern (MID)

AF:

0.455

AC:

1179

AN:

2594

European-Non Finnish (NFE)

AF:

0.378

AC:

195650

AN:

517226

Other (OTH)

AF:

0.397

AC:

14254

AN:

35944

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

9932

19863

29795

39726

49658

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.354

AC:

53708

AN:

151910

Hom.:

10128

Cov.:

AF XY:

0.356

AC XY:

26436

AN XY:

74244

show subpopulations

African (AFR)

AF:

0.239

AC:

9910

AN:

41424

American (AMR)

AF:

0.389

AC:

5942

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.404

AC:

1393

AN:

3450

East Asian (EAS)

AF:

0.595

AC:

3057

AN:

5138

South Asian (SAS)

AF:

0.549

AC:

2641

AN:

4808

European-Finnish (FIN)

AF:

0.368

AC:

3886

AN:

10564

Middle Eastern (MID)

AF:

0.429

AC:

126

AN:

294

European-Non Finnish (NFE)

AF:

0.378

AC:

25700

AN:

67932

Other (OTH)

AF:

0.377

AC:

795

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1725

3450

5174

6899

8624

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

(source)

DANN

Benign

0.46

PhyloP100

-1.2

PromoterAI

0.049

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-G

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