Genetic Variant HSPD1:p.Gly571_Met572insMetGlyGlyGly (chr2-197487055-G-GCCACCTCCCATA) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_002156.5(HSPD1):c.1701_1712dupTATGGGAGGTGG(p.Gly571_Met572insMetGlyGlyGly) variant causes a disruptive inframe insertion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000023 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HSPD1
NM_002156.5 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.20

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_002156.5.

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	HGVSp	Effect	Exon Rank	Protein	UniProt
HSPD1	NM_002156.5	MANE Select	c.1701_1712dupTATGGGAGGTGG	p.Gly571_Met572insMetGlyGlyGly	disruptive_inframe_insertion	Exon 12 of 12	NP_002147.2
HSPD1	NM_199440.2		c.1701_1712dupTATGGGAGGTGG	p.Gly571_Met572insMetGlyGlyGly	disruptive_inframe_insertion	Exon 12 of 12	NP_955472.1	A0A024R3X4
SNORA105B	NR_132788.1		n.-164_-153dupTATGGGAGGTGG		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HSPD1	ENST00000388968.8	TSL:1 MANE Select	c.1701_1712dupTATGGGAGGTGG	p.Gly571_Met572insMetGlyGlyGly	disruptive_inframe_insertion	Exon 12 of 12	ENSP00000373620.3	P10809-1
HSPD1	ENST00000954440.1		c.1749_1760dupTATGGGAGGTGG	p.Gly587_Met588insMetGlyGlyGly	disruptive_inframe_insertion	Exon 12 of 12	ENSP00000624499.1
HSPD1	ENST00000345042.6	TSL:5	c.1701_1712dupTATGGGAGGTGG	p.Gly571_Met572insMetGlyGlyGly	disruptive_inframe_insertion	Exon 12 of 12	ENSP00000340019.2	P10809-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000406

AC:

AN:

246332

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000901

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000229

AC:

AN:

1310624

Hom.:

Cov.:

AF XY:

0.00000152

AC XY:

AN XY:

659980

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30606

American (AMR)

AF:

0.00

AC:

AN:

44470

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25124

East Asian (EAS)

AF:

0.00

AC:

AN:

38916

South Asian (SAS)

AF:

0.00

AC:

AN:

83232

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53328

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5360

European-Non Finnish (NFE)

AF:

0.00000205

AC:

AN:

974240

Other (OTH)

AF:

0.0000181

AC:

AN:

55348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

7.2

Splicing

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

Publications

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2-197487055-GCCACCTCCCATA-GCCACCTCCCATACCACCTCCCATA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over