rs1438601135

Variant names:

• chr2-197487067-A-G
• rs1438601135
• NM_002156.5:c.1701T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-197487067-A-G
• chr2-197487067-A-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_002156.5(HSPD1):​c.1701T>C​(p.Gly567Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000737 in 1,355,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: HSPD1 NM_002156.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.43
• 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 2-197487067-A-G is Benign according to our data. Variant chr2-197487067-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2083046.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.43 with no splicing effect.

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.1701T>C	p.Gly567Gly	synonymous	Exon 12 of 12	NP_002147.2
	HSPD1	NM_199440.2		c.1701T>C	p.Gly567Gly	synonymous	Exon 12 of 12	NP_955472.1	A0A024R3X4
	SNORA105B	NR_132788.1		n.-164T>C		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.1701T>C	p.Gly567Gly	synonymous	Exon 12 of 12	ENSP00000373620.3	P10809-1
	HSPD1	ENST00000954440.1		c.1749T>C	p.Gly583Gly	synonymous	Exon 12 of 12	ENSP00000624499.1
	HSPD1	ENST00000345042.6	TSL:5	c.1701T>C	p.Gly567Gly	synonymous	Exon 12 of 12	ENSP00000340019.2	P10809-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.37e-7 AC: 1 AN: 1355994 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 680610

African (AFR) AF: 0.00 AC: 0 AN: 31374

American (AMR) AF: 0.00 AC: 0 AN: 44526

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25490

East Asian (EAS) AF: 0.00 AC: 0 AN: 39214

South Asian (SAS) AF: 0.0000119 AC: 1 AN: 84196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5528

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1015620

Other (OTH) AF: 0.00 AC: 0 AN: 56698

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Spastic paraplegia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.54
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism

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: rs1438601135; hg19: chr2-198351791;