1-156743799-G-T

Variant names:

• chr1-156743799-G-T
• rs1650307978
• NM_004494.3:c.569C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004494.3(HDGF):​c.569C>A​(p.Pro190His) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P190R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HDGF NM_004494.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.35
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22255117).

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.569C>A	p.Pro190His	missense	Exon 5 of 6	NP_004485.1	P51858-1
	HDGF	NM_001319186.2		c.638C>A	p.Pro213His	missense	Exon 5 of 6	NP_001306115.1
	HDGF	NM_001126050.2		c.617C>A	p.Pro206His	missense	Exon 5 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.569C>A	p.Pro190His	missense	Exon 5 of 6	ENSP00000349878.5	P51858-1
	HDGF	ENST00000465180.5	TSL:1	n.983C>A		non_coding_transcript_exon	Exon 7 of 8
	HDGF	ENST00000710272.1		c.824C>A	p.Pro275His	missense	Exon 5 of 6	ENSP00000518165.1	A0AA34QVG5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		3.4
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.067
Sift	Benign	0.14	T
Sift4G	Benign	0.20	T
Polyphen		0.99	D
Vest4		0.32
MutPred		0.22		Gain of sheet (P = 0.0221)
MVP		0.60
MPC		1.3
ClinPred		0.92	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.21
Mutation Taster		=79/21	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

dbSNP: rs1650307978; hg19: chr1-156713591;