Genetic Variant HDGF:p.Ala153Gly (chr1-156744194-G-C) – 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 NM_004494.3(HDGF):c.458C>G(p.Ala153Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A153V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

HDGF
NM_004494.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.23

Publications

2 publications found

Variant links:

Genes affected

HDGF (HGNC:4856): (heparin binding growth factor) This gene encodes a member of the hepatoma-derived growth factor family. The encoded protein has mitogenic and DNA-binding activity and may play a role in cellular proliferation and differentiation. High levels of expression of this gene enhance the growth of many tumors. This gene was thought initially to be located on chromosome X; however, that location has been determined to correspond to a related pseudogene. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jan 2016]

HDGF 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 (MetaRNN=0.037459373).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004494.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HDGF	NM_004494.3	MANE Select	c.458C>G	p.Ala153Gly	missense	Exon 4 of 6	NP_004485.1	P51858-1
HDGF	NM_001319186.2		c.527C>G	p.Ala176Gly	missense	Exon 4 of 6	NP_001306115.1
HDGF	NM_001126050.2		c.506C>G	p.Ala169Gly	missense	Exon 4 of 6	NP_001119522.1	P51858-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HDGF	ENST00000357325.10	TSL:1 MANE Select	c.458C>G	p.Ala153Gly	missense	Exon 4 of 6	ENSP00000349878.5	P51858-1
HDGF	ENST00000465180.5	TSL:1	n.872C>G		non_coding_transcript_exon	Exon 6 of 8
HDGF	ENST00000710272.1		c.713C>G	p.Ala238Gly	missense	Exon 4 of 6	ENSP00000518165.1	A0AA34QVG5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251478

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.016

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.46

M_CAP

Benign

0.0053

MetaRNN

Benign

0.037

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.3

PhyloP100

1.2

PrimateAI

Benign

0.37

PROVEAN

Benign

0.18

REVEL

Benign

0.028

Sift

Benign

0.50

Sift4G

Benign

0.95

Polyphen

0.0010

Vest4

0.059

MutPred

0.098

Loss of stability (P = 0.1061)

MVP

0.31

MPC

0.44

ClinPred

0.039

GERP RS

2.2

Varity_R

0.036

gMVP

0.15

Mutation Taster

=90/10

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over