chr14-99657097-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001127258.3(HHIPL1):c.1000G>A(p.Gly334Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000471 in 1,613,386 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000047 ( 0 hom. )
Consequence
HHIPL1
NM_001127258.3 missense
NM_001127258.3 missense
Scores
11
4
4
Clinical Significance
Conservation
PhyloP100: 9.91
Genes affected
HHIPL1 (HGNC:19710): (HHIP like 1) This gene encodes a protein that belongs to the glucose/sorbosone dehydrogenase family. The encoded protein also contains a domain that binds folate and reduced folic acid derivatives. [provided by RefSeq, Jul 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.849
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HHIPL1 | NM_001127258.3 | c.1000G>A | p.Gly334Arg | missense_variant | 3/9 | ENST00000330710.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HHIPL1 | ENST00000330710.10 | c.1000G>A | p.Gly334Arg | missense_variant | 3/9 | 1 | NM_001127258.3 | P1 | |
HHIPL1 | ENST00000357223.2 | c.1000G>A | p.Gly334Arg | missense_variant | 3/8 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152078Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000136 AC: 34AN: 250470Hom.: 0 AF XY: 0.000133 AC XY: 18AN XY: 135408
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GnomAD4 exome AF: 0.0000472 AC: 69AN: 1461308Hom.: 0 Cov.: 31 AF XY: 0.0000592 AC XY: 43AN XY: 726946
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GnomAD4 genome AF: 0.0000460 AC: 7AN: 152078Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74282
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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 | Dec 13, 2022 | The c.1000G>A (p.G334R) alteration is located in exon 3 (coding exon 3) of the HHIPL1 gene. This alteration results from a G to A substitution at nucleotide position 1000, causing the glycine (G) at amino acid position 334 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
H;H
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MutPred
Gain of methylation at G334 (P = 0.0144);Gain of methylation at G334 (P = 0.0144);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at