Genetic Variant HSPD1:c.*18dupT (chr2-197487027-T-TA) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP6

The NM_002156.5(HSPD1):c.*18dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000106 in 1,167,456 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000087 ( 0 hom. )

Consequence

HSPD1
NM_002156.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.939

Publications

0 publications found

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]

HSPD1 links:

SNORA105B (HGNC:51398): (small nucleolar RNA, H/ACA box 105B)

SNORA105B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP6

Variant 2-197487027-T-TA is Benign according to our data. Variant chr2-197487027-T-TA is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 333305.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002156.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HSPD1	NM_002156.5	MANE Select	c.*18dupT	3_prime_UTR	Exon 12 of 12	NP_002147.2
HSPD1	NM_199440.2		c.*18dupT	3_prime_UTR	Exon 12 of 12	NP_955472.1	A0A024R3X4
SNORA105B	NR_132788.1		n.-125dupT	upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HSPD1	ENST00000388968.8	TSL:1 MANE Select	c.*18dupT	3_prime_UTR	Exon 12 of 12	ENSP00000373620.3	P10809-1
HSPD1	ENST00000954440.1		c.*18dupT	3_prime_UTR	Exon 12 of 12	ENSP00000624499.1
HSPD1	ENST00000345042.6	TSL:5	c.*18dupT	3_prime_UTR	Exon 12 of 12	ENSP00000340019.2	P10809-1

Frequencies

GnomAD3 genomes

AF:

0.000237

AC:

AN:

152016

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00171

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:

0.0000735

Gnomad OTH

AF:

0.000958

GnomAD2 exomes

AF:

0.0000863

AC:

AN:

243216

AF XY:

0.0000829

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000411

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000549

Gnomad OTH exome

AF:

0.000168

GnomAD4 exome

AF:

0.0000867

AC:

AN:

1015322

Hom.:

Cov.:

AF XY:

0.0000821

AC XY:

AN XY:

523848

show subpopulations

African (AFR)

AF:

0.0000813

AC:

AN:

24592

American (AMR)

AF:

0.000570

AC:

AN:

43872

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23244

East Asian (EAS)

AF:

0.00

AC:

AN:

37716

South Asian (SAS)

AF:

0.00

AC:

AN:

77152

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53038

Middle Eastern (MID)

AF:

0.000234

AC:

AN:

4274

European-Non Finnish (NFE)

AF:

0.0000779

AC:

AN:

705748

Other (OTH)

AF:

0.000109

AC:

AN:

45686

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000237

AC:

AN:

152134

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.0000723

AC:

AN:

41500

American (AMR)

AF:

0.00170

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

67996

Other (OTH)

AF:

0.000948

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000446

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Spastic paraplegia, autosomal dominant (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.94

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over