2-197487066-T-C

Variant summary

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

The NM_002156.5(HSPD1):​c.1702A>G​(p.Met568Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000464 in 1,508,944 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000037 ( 0 hom. )

Consequence

HSPD1
NM_002156.5 missense

Scores

4
8
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.45
Variant links:
Genes affected
HSPD1 (HGNC:5261): (heat shock protein family D (Hsp60) member 1) This gene encodes a member of the chaperonin family. The encoded mitochondrial protein may function as a signaling molecule in the innate immune system. This protein is essential for the folding and assembly of newly imported proteins in the mitochondria. This gene is adjacent to a related family member and the region between the 2 genes functions as a bidirectional promoter. Several pseudogenes have been associated with this gene. Two transcript variants encoding the same protein have been identified for this gene. Mutations associated with this gene cause autosomal recessive spastic paraplegia 13. [provided by RefSeq, Jun 2010]
SNORA105B (HGNC:51398): (small nucleolar RNA, H/ACA box 105B)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HSPD1NM_002156.5 linkc.1702A>G p.Met568Val missense_variant Exon 12 of 12 ENST00000388968.8 NP_002147.2 P10809-1A0A024R3X4
HSPD1NM_199440.2 linkc.1702A>G p.Met568Val missense_variant Exon 12 of 12 NP_955472.1 P10809-1A0A024R3X4
SNORA105BNR_132788.1 linkn.-163A>G upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HSPD1ENST00000388968.8 linkc.1702A>G p.Met568Val missense_variant Exon 12 of 12 1 NM_002156.5 ENSP00000373620.3 P10809-1

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
152070
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000656
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000122
AC:
3
AN:
246882
Hom.:
0
AF XY:
0.0000149
AC XY:
2
AN XY:
134460
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000180
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000368
AC:
5
AN:
1356874
Hom.:
0
Cov.:
21
AF XY:
0.00000587
AC XY:
4
AN XY:
680940
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000225
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000394
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
152070
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74286
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000656
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Spastic paraplegia Uncertain:1
Oct 15, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 568 of the HSPD1 protein (p.Met568Val). This variant is present in population databases (rs757331948, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with HSPD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1415601). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.32
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Uncertain
0.10
CADD
Uncertain
23
DANN
Benign
0.95
DEOGEN2
Pathogenic
0.84
D;D
Eigen
Uncertain
0.23
Eigen_PC
Uncertain
0.36
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.69
.;T
M_CAP
Benign
0.053
D
MetaRNN
Uncertain
0.58
D;D
MetaSVM
Benign
-0.45
T
MutationAssessor
Pathogenic
3.6
H;H
PrimateAI
Uncertain
0.69
T
PROVEAN
Uncertain
-2.6
D;D
REVEL
Uncertain
0.59
Sift
Benign
0.30
T;T
Sift4G
Uncertain
0.019
D;D
Polyphen
0.32
B;B
Vest4
0.65
MutPred
0.45
Gain of catalytic residue at M568 (P = 0.0721);Gain of catalytic residue at M568 (P = 0.0721);
MVP
0.72
MPC
1.9
ClinPred
0.38
T
GERP RS
5.2
Varity_R
0.33
gMVP
0.80

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

LitVar

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

Other links and lift over

dbSNP: rs757331948; hg19: chr2-198351790; API