chr9-133356647-C-A

Variant names:

• chr9-133356647-C-A
• rs782207218
• NM_017503.5:c.55C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_017503.5(SURF2):​c.55C>A​(p.Arg19Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SURF2 NM_017503.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.676
• Publications: 0 publications found

Genes affected

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]

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]

SURF1 Gene-Disease associations (from GenCC):

• Leigh syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
• mitochondrial complex IV deficiency, nuclear type 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, G2P
• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Charcot-Marie-Tooth disease type 4K

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae)
• Leigh syndrome with cardiomyopathy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Leigh syndrome with leukodystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP7: Synonymous conserved (PhyloP=0.676 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017503.5. 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
	SURF2	NM_017503.5	MANE Select	c.55C>A	p.Arg19Arg	synonymous	Exon 1 of 6	NP_059973.4
	SURF2	NM_001278928.2		c.55C>A	p.Arg19Arg	synonymous	Exon 1 of 6	NP_001265857.1
	SURF1	NM_003172.4	MANE Select	c.-194G>T		upstream_gene	N/A	NP_003163.1	Q15526-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SURF2	ENST00000371964.5	TSL:1 MANE Select	c.55C>A	p.Arg19Arg	synonymous	Exon 1 of 6	ENSP00000361032.4	Q15527
	SURF2	ENST00000934438.1		c.55C>A	p.Arg19Arg	synonymous	Exon 1 of 7	ENSP00000604497.1
	SURF2	ENST00000875735.1		c.55C>A	p.Arg19Arg	synonymous	Exon 1 of 6	ENSP00000545794.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1372782 Hom.: 0 Cov.: 38 AF XY: 0.00 AC XY: 0 AN XY: 677358

African (AFR) AF: 0.00 AC: 0 AN: 29880

American (AMR) AF: 0.00 AC: 0 AN: 34820

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24600

East Asian (EAS) AF: 0.00 AC: 0 AN: 34520

South Asian (SAS) AF: 0.00 AC: 0 AN: 78294

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33700

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4676

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1074930

Other (OTH) AF: 0.00 AC: 0 AN: 57362

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	14
DANN	Benign	0.80
PhyloP100		0.68
PromoterAI		0.022	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs782207218; hg19: chr9-136223523;