rs12335

Variant names:

• chr9-133330998-A-G
• rs12335
• NM_006753.6:c.*871T>C

Variant summary

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

The NM_006753.6(SURF6):​c.*871T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 152,030 control chromosomes in the GnomAD database, including 21,588 homozygotes. 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: 𝑓 0.53 (21587 hom., cov: 32)
  • Exomes 𝑓: 0.58 (1 hom.)
• Consequence: SURF6 NM_006753.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.978

Genes affected

SURF6 (HGNC:11478): (surfeit 6) This gene encodes a conserved protein that is localized to the nucleolus. The encoded protein may function as a nucleolar-matrix protein with nucleic acid-binding properties. There is a pseudogene for this gene on chromosome Y. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SURF6	NM_006753.6	c.*871T>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000372022.6	NP_006744.2
SURF6	NM_001278942.2	c.*1362T>C		3_prime_UTR_variant	Exon 5 of 5		NP_001265871.1
SURF6	NR_103874.2	n.1960T>C		non_coding_transcript_exon_variant	Exon 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SURF6	ENST00000372022	c.*871T>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_006753.6	ENSP00000361092.4

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80350 AN: 151900 Hom.: 21553 Cov.: 32

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.484

GnomAD4 exome AF: 0.583 AC: 7 AN: 12 Hom.: 1 Cov.: 0 AF XY: 0.667 AC XY: 4 AN XY: 6

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.625

GnomAD4 genome AF: 0.529 AC: 80432 AN: 152018 Hom.: 21587 Cov.: 32 AF XY: 0.531 AC XY: 39472 AN XY: 74296

Gnomad4 AFR AF: 0.584

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.406

Gnomad4 EAS AF: 0.342

Gnomad4 SAS AF: 0.510

Gnomad4 FIN AF: 0.604

Gnomad4 NFE AF: 0.524

Gnomad4 OTH AF: 0.481

Alfa AF: 0.520 Hom.: 4693

Bravo AF: 0.516

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.41

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12335; hg19: chr9-136197834;