rs587598397

Variant names:

• chr9-133356390-C-G
• rs587598397
• NM_003172.4:c.54+10G>C

Your query was ambiguous. Multiple possible variants found:

• chr9-133356390-C-G
• chr9-133356390-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_003172.4(SURF1):​c.54+10G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000161 in 1,238,642 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: 34)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: SURF1 NM_003172.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.389
• Publications: 0 publications found

Genes affected

SURF1 (HGNC:11474): (SURF1 cytochrome c oxidase assembly factor) This gene encodes a protein localized to the inner mitochondrial membrane and thought to be involved in the biogenesis of the cytochrome c oxidase complex. The protein is a member of the SURF1 family, which includes the related yeast protein SHY1 and rickettsial protein RP733. The gene is located in the surfeit gene cluster, a group of very tightly linked genes that do not share sequence similarity, where it shares a bidirectional promoter with SURF2 on the opposite strand. Defects in this gene are a cause of Leigh syndrome, a severe neurological disorder that is commonly associated with systemic cytochrome c oxidase deficiency. [provided by RefSeq, Jul 2008]

SURF2 (HGNC:11475): (surfeit 2) This gene shares a bidirectional promoter with surfeit 1 (SURF1; GeneID: 6834), which is located on the opposite strand. It encodes a conserved protein that is expressed in a variety of tissues. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 9-133356390-C-G is Benign according to our data. Variant chr9-133356390-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2984476.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003172.4. 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
	SURF1	NM_003172.4	MANE Select	c.54+10G>C		intron	N/A	NP_003163.1	Q15526-1
	SURF1	NM_001280787.1		c.-222+10G>C		intron	N/A	NP_001267716.1	A0A087WYS9
	SURF2	NM_017503.5	MANE Select	c.-203C>G		upstream_gene	N/A	NP_059973.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SURF1	ENST00000371974.8	TSL:1 MANE Select	c.54+10G>C		intron	N/A	ENSP00000361042.3	Q15526-1
	SURF1	ENST00000615505.4	TSL:1	c.-222+10G>C		intron	N/A	ENSP00000482067.1	A0A087WYS9
	SURF1	ENST00000886676.1		c.54+10G>C		intron	N/A	ENSP00000556735.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000161 AC: 2 AN: 1238642 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 607026

African (AFR) AF: 0.00 AC: 0 AN: 24364

American (AMR) AF: 0.00 AC: 0 AN: 16130

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18996

East Asian (EAS) AF: 0.0000737 AC: 2 AN: 27132

South Asian (SAS) AF: 0.00 AC: 0 AN: 59020

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3538

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1008318

Other (OTH) AF: 0.00 AC: 0 AN: 50912

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Leigh syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.8
DANN	Benign	0.53
PhyloP100		0.39
PromoterAI		-0.021	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs587598397; hg19: chr9-136223266;