chr4-56650812-C-A
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_032495.6(HOPX):c.199-2015G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000324 in 1,543,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000022 ( 0 hom. )
Consequence
HOPX
NM_032495.6 intron
NM_032495.6 intron
Scores
15
Splicing: ADA: 0.5459
2
Clinical Significance
Conservation
PhyloP100: -0.0750
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.04544881).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HOPX | NM_032495.6 | c.199-2015G>T | intron_variant | ENST00000420433.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HOPX | ENST00000420433.6 | c.199-2015G>T | intron_variant | 5 | NM_032495.6 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152082Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000216 AC: 3AN: 1391770Hom.: 0 Cov.: 31 AF XY: 0.00000146 AC XY: 1AN XY: 686070
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GnomAD4 genome AF: 0.0000132 AC: 2AN: 152082Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74270
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 25, 2023 | The c.199G>T (p.G67C) alteration is located in exon 4 (coding exon 3) of the HOPX gene. This alteration results from a G to T substitution at nucleotide position 199, causing the glycine (G) at amino acid position 67 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Vest4
MVP
MPC
ClinPred
T
GERP RS
gMVP
Splicing
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Calibrated prediction
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at