dbSNP rs483353075: HOPX:p.Val42Leu (chr4-56655931-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032495.6(HOPX):c.124G>C(p.Val42Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

HOPX
NM_032495.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.17

Variant links:

Genes affected

HOPX (HGNC:24961): (HOP homeobox) The protein encoded by this gene is a homeodomain protein that lacks certain conserved residues required for DNA binding. It was reported that choriocarcinoma cell lines and tissues failed to express this gene, which suggested the possible involvement of this gene in malignant conversion of placental trophoblasts. Studies in mice suggest that this protein may interact with serum response factor (SRF) and modulate SRF-dependent cardiac-specific gene expression and cardiac development. Multiple alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Feb 2009]

HOPX links:

LOC124900708 (HGNC:):

LOC124900708 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1502198).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOPX	NM_032495.6 link	c.124G>C	p.Val42Leu	missense_variant	Exon 3 of 4	ENST00000420433.6	NP_115884.4	Q9BPY8-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOPX	ENST00000420433.6 link	c.124G>C	p.Val42Leu	missense_variant	Exon 3 of 4	5	NM_032495.6	ENSP00000396275.1		Q9BPY8-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459614

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725938

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.086

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Uncertain

0.63

.;D;.;D;D;D;D;D;D;D;.;D

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.83

T;.;T;.;.;.;.;.;.;.;T;T

M_CAP

Benign

0.048

MetaRNN

Benign

0.15

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.96

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.2

N;N;N;N;N;N;N;N;N;N;N;.

REVEL

Benign

0.045

Sift

Benign

0.17

T;T;D;T;T;T;T;T;T;T;T;.

Sift4G

Uncertain

0.039

D;T;D;T;T;T;T;T;T;T;D;T

Polyphen

0.0030

.;B;.;B;B;B;B;B;B;B;.;B

Vest4

0.28

MutPred

0.35

.;Loss of methylation at K23 (P = 0.0532);.;Loss of methylation at K23 (P = 0.0532);Loss of methylation at K23 (P = 0.0532);Loss of methylation at K23 (P = 0.0532);Loss of methylation at K23 (P = 0.0532);Loss of methylation at K23 (P = 0.0532);Loss of methylation at K23 (P = 0.0532);Loss of methylation at K23 (P = 0.0532);Loss of methylation at K23 (P = 0.0532);Loss of methylation at K23 (P = 0.0532);

MVP

0.41

MPC

0.39

ClinPred

0.92

GERP RS

3.8

Varity_R

0.18

gMVP

0.39

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over