rs1347832996

Variant names:

• chr2-197487080-CCACCCATTG-C
• rs1347832996
• NM_002156.5:c.1679_1687delCAATGGGTG

Your query was ambiguous. Multiple possible variants found:

• chr2-197487080-CCACCCATTG-C
• chr2-197487080-CCACCCATTG-CCACCCATTGCACCCATTG

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2 PM4 PP3

The NM_002156.5(HSPD1):​c.1679_1687delCAATGGGTG​(p.Ala560_Gly562del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HSPD1 NM_002156.5 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.68
• 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]

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_002156.5.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.1679_1687delCAATGGGTG	p.Ala560_Gly562del	disruptive_inframe_deletion	Exon 12 of 12	NP_002147.2
	HSPD1	NM_199440.2		c.1679_1687delCAATGGGTG	p.Ala560_Gly562del	disruptive_inframe_deletion	Exon 12 of 12	NP_955472.1	A0A024R3X4
	SNORA105B	NR_132788.1		n.-186_-178delCAATGGGTG		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPD1	ENST00000388968.8	TSL:1 MANE Select	c.1679_1687delCAATGGGTG	p.Ala560_Gly562del	disruptive_inframe_deletion	Exon 12 of 12	ENSP00000373620.3	P10809-1
	HSPD1	ENST00000954440.1		c.1727_1735delCAATGGGTG	p.Ala576_Gly578del	disruptive_inframe_deletion	Exon 12 of 12	ENSP00000624499.1
	HSPD1	ENST00000345042.6	TSL:5	c.1679_1687delCAATGGGTG	p.Ala560_Gly562del	disruptive_inframe_deletion	Exon 12 of 12	ENSP00000340019.2	P10809-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000405 AC: 1 AN: 246966 AF XY: 0.00000743

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000547

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000102 AC: 14 AN: 1375082 Hom.: 0 AF XY: 0.00000726 AC XY: 5 AN XY: 689084

African (AFR) AF: 0.00 AC: 0 AN: 31648

American (AMR) AF: 0.00 AC: 0 AN: 44550

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25608

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39300

South Asian (SAS) AF: 0.0000236 AC: 2 AN: 84570

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53372

Middle Eastern (MID) AF: 0.000537 AC: 3 AN: 5590

European-Non Finnish (NFE) AF: 0.00000774 AC: 8 AN: 1032974

Other (OTH) AF: 0.00 AC: 0 AN: 57470

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.7

Splicing

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

Other links and lift over

dbSNP: rs1347832996; hg19: chr2-198351804;