rs12763

Positions:

• chr9-133360384-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017503.5(SURF2):​c.637G>A​(p.Gly213Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 1,612,964 control chromosomes in the GnomAD database, including 121,454 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.33 (9154 hom., cov: 33)
  • Exomes 𝑓: 0.39 (112300 hom.)
• Consequence: SURF2 NM_017503.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0870

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0023717284).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SURF2	NM_017503.5	c.637G>A	p.Gly213Ser	missense_variant	5/6	ENST00000371964.5	NP_059973.4
SURF2	NM_001278928.2	c.637G>A	p.Gly213Ser	missense_variant	5/6		NP_001265857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SURF2	ENST00000371964.5	c.637G>A	p.Gly213Ser	missense_variant	5/6	1	NM_017503.5	ENSP00000361032	P1

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50582 AN: 151944 Hom.: 9148 Cov.: 33

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.307

GnomAD4 exome AF: 0.388 AC: 566908 AN: 1460902 Hom.: 112300 Cov.: 58 AF XY: 0.391 AC XY: 284046 AN XY: 726702

Gnomad4 AFR exome AF: 0.204

Gnomad4 AMR exome AF: 0.373

Gnomad4 ASJ exome AF: 0.266

Gnomad4 EAS exome AF: 0.319

Gnomad4 SAS exome AF: 0.465

Gnomad4 FIN exome AF: 0.470

Gnomad4 NFE exome AF: 0.392

Gnomad4 OTH exome AF: 0.366

GnomAD4 genome AF: 0.333 AC: 50586 AN: 152062 Hom.: 9154 Cov.: 33 AF XY: 0.337 AC XY: 25078 AN XY: 74308

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.322

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.460

Gnomad4 NFE AF: 0.389

Gnomad4 OTH AF: 0.305

Alfa AF: 0.373 Hom.: 5522

Bravo AF: 0.311

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
MetaRNN	Benign	0.0024	T
Sift4G	Benign	1.0	T
Vest4		0.043
gMVP		0.052

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12763; hg19: chr9-136227260;