rs788016

Variant names:

• chr2-197487569-G-A
• rs788016
• NM_002156.5:c.1569+289C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002156.5(HSPD1):​c.1569+289C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 152,034 control chromosomes in the GnomAD database, including 14,007 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.42 (14007 hom., cov: 32)
• Consequence: HSPD1 NM_002156.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.310
• Publications: 23 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: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hypomyelinating leukodystrophy 4

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

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.1569+289C>T		intron	N/A	NP_002147.2
	HSPD1	NM_199440.2		c.1569+289C>T		intron	N/A	NP_955472.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPD1	ENST00000388968.8	TSL:1 MANE Select	c.1569+289C>T		intron	N/A	ENSP00000373620.3
	HSPD1	ENST00000954440.1		c.1617+289C>T		intron	N/A	ENSP00000624499.1
	HSPD1	ENST00000345042.6	TSL:5	c.1569+289C>T		intron	N/A	ENSP00000340019.2

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63895 AN: 151916 Hom.: 14017 Cov.: 32

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.438

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.420 AC: 63882 AN: 152034 Hom.: 14007 Cov.: 32 AF XY: 0.419 AC XY: 31127 AN XY: 74310

African (AFR) AF: 0.323 AC: 13392 AN: 41482

American (AMR) AF: 0.406 AC: 6201 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1760 AN: 3470

East Asian (EAS) AF: 0.263 AC: 1361 AN: 5182

South Asian (SAS) AF: 0.563 AC: 2710 AN: 4812

European-Finnish (FIN) AF: 0.387 AC: 4080 AN: 10554

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32830 AN: 67964

Other (OTH) AF: 0.434 AC: 916 AN: 2110

Alfa AF: 0.472 Hom.: 29886

Bravo AF: 0.410

Asia WGS AF: 0.393 AC: 1373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.7
DANN	Benign	0.93
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs788016; hg19: chr2-198352293;