22-17138338-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_033070.3(HDHD5):​c.955G>A​(p.Val319Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000564 in 1,613,546 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

HDHD5
NM_033070.3 missense

Scores

18

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0240
Variant links:
Genes affected
HDHD5 (HGNC:1843): (haloacid dehalogenase like hydrolase domain containing 5) Predicted to be involved in glycerophospholipid biosynthetic process. Predicted to be active in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.026051432).
BP6
Variant 22-17138338-C-T is Benign according to our data. Variant chr22-17138338-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2465950.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HDHD5NM_033070.3 linkc.955G>A p.Val319Ile missense_variant Exon 8 of 8 ENST00000336737.8 NP_149061.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HDHD5ENST00000336737.8 linkc.955G>A p.Val319Ile missense_variant Exon 8 of 8 1 NM_033070.3 ENSP00000337358.4 Q9BXW7-1

Frequencies

GnomAD3 genomes
AF:
0.000125
AC:
19
AN:
152138
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.000829
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000957
GnomAD3 exomes
AF:
0.000117
AC:
29
AN:
247812
Hom.:
0
AF XY:
0.0000968
AC XY:
13
AN XY:
134254
show subpopulations
Gnomad AFR exome
AF:
0.000126
Gnomad AMR exome
AF:
0.000203
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000458
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000361
Gnomad OTH exome
AF:
0.000329
GnomAD4 exome
AF:
0.0000493
AC:
72
AN:
1461408
Hom.:
0
Cov.:
31
AF XY:
0.0000660
AC XY:
48
AN XY:
726992
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
Gnomad4 AMR exome
AF:
0.000246
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000336
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000180
Gnomad4 OTH exome
AF:
0.000166
GnomAD4 genome
AF:
0.000125
AC:
19
AN:
152138
Hom.:
0
Cov.:
32
AF XY:
0.0000673
AC XY:
5
AN XY:
74314
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000829
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000957
Alfa
AF:
0.0000868
Hom.:
0
Bravo
AF:
0.000215
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000989
AC:
12
Asia WGS
AF:
0.00173
AC:
6
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Feb 16, 2023
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.070
BayesDel_addAF
Benign
-0.51
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
0.20
DANN
Benign
0.31
DEOGEN2
Benign
0.037
.;T;.
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.069
N
LIST_S2
Benign
0.80
T;T;T
M_CAP
Benign
0.0053
T
MetaRNN
Benign
0.026
T;T;T
MetaSVM
Benign
-0.94
T
PrimateAI
Benign
0.26
T
PROVEAN
Benign
0.38
N;N;N
REVEL
Benign
0.084
Sift
Benign
1.0
T;T;T
Sift4G
Benign
1.0
T;T;T
Polyphen
0.013
B;B;B
Vest4
0.089
MVP
0.030
MPC
0.15
ClinPred
0.0022
T
GERP RS
-0.049
Varity_R
0.0096
gMVP
0.31

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs142416632; hg19: chr22-17619228; COSMIC: COSV50095337; API