HSPD1 p.Lys91Lys

Variant names:

• chr2-197497293-T-T
• NM_002156.5:c.

Your query was ambiguous. Multiple possible variants found:

• chr2-197497294--
• chr2-197497294-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002156.5(HSPD1):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: HSPD1 NM_002156.5 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.897
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• hereditary spastic paraplegia 13

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• hypomyelinating leukodystrophy 4

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPD1	NM_002156.5	MANE Select	c.		exon_region	Exon 3 of 12	NP_002147.2
	HSPD1	NM_199440.2		c.		exon_region	Exon 3 of 12	NP_955472.1	A0A024R3X4

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.90

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-198362017;