1-156745012-T-C

Variant names:

• chr1-156745012-T-C
• NM_004494.3:c.299A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004494.3(HDGF):​c.299A>G​(p.Tyr100Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: HDGF NM_004494.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.66
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29104638).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDGF	NM_004494.3	MANE Select	c.299A>G	p.Tyr100Cys	missense	Exon 3 of 6	NP_004485.1	P51858-1
	HDGF	NM_001319186.2		c.347A>G	p.Tyr116Cys	missense	Exon 3 of 6	NP_001306115.1
	HDGF	NM_001126050.2		c.347A>G	p.Tyr116Cys	missense	Exon 3 of 6	NP_001119522.1	P51858-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDGF	ENST00000357325.10	TSL:1 MANE Select	c.299A>G	p.Tyr100Cys	missense	Exon 3 of 6	ENSP00000349878.5	P51858-1
	HDGF	ENST00000465180.5	TSL:1	n.713A>G		non_coding_transcript_exon	Exon 5 of 8
	HDGF	ENST00000710272.1		c.554A>G	p.Tyr185Cys	missense	Exon 3 of 6	ENSP00000518165.1	A0AA34QVG5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	1.3	L
PhyloP100		4.7
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.29
Sift	Benign	0.22	T
Sift4G	Benign	0.16	T
Polyphen		0.97	D
Vest4		0.31
MutPred		0.20		Loss of phosphorylation at Y100 (P = 0.0205)
MVP		0.81
MPC		1.4
ClinPred		0.98	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.41
gMVP		0.70
Mutation Taster		=53/47	polymorphism

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

Other links and lift over

hg19: chr1-156714804; COSMIC: COSV61975972; COSMIC: COSV61975972;