9-133332667-G-A

Position:

• chr9-133332667-G-A

Variant summary

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

The NM_006753.6(SURF6):​c.487C>T​(p.Arg163Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 1,611,800 control chromosomes in the GnomAD database, including 105,839 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.28 (7506 hom., cov: 33)
  • Exomes 𝑓: 0.36 (98333 hom.)
• Consequence: SURF6 NM_006753.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.374

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 (MetaRNN=0.0018672347).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SURF6	NM_006753.6	c.487C>T	p.Arg163Trp	missense_variant	4/5	ENST00000372022.6	NP_006744.2
SURF6	NM_001278942.2	c.486C>T	p.Cys162=	synonymous_variant	4/5		NP_001265871.1
SURF6	NR_103874.2	n.490C>T		non_coding_transcript_exon_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SURF6	ENST00000372022.6	c.487C>T	p.Arg163Trp	missense_variant	4/5	1	NM_006753.6	ENSP00000361092	P1
SURF6	ENST00000468290.1	n.273C>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42813 AN: 152016 Hom.: 7499 Cov.: 33

Gnomad AFR AF: 0.0746

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.265

GnomAD3 exomes AF: 0.354 AC: 88342 AN: 249896 Hom.: 16883 AF XY: 0.362 AC XY: 48978 AN XY: 135328

Gnomad AFR exome AF: 0.0725

Gnomad AMR exome AF: 0.358

Gnomad ASJ exome AF: 0.234

Gnomad EAS exome AF: 0.334

Gnomad SAS exome AF: 0.460

Gnomad FIN exome AF: 0.454

Gnomad NFE exome AF: 0.360

Gnomad OTH exome AF: 0.345

GnomAD4 exome AF: 0.361 AC: 526451 AN: 1459666 Hom.: 98333 Cov.: 54 AF XY: 0.365 AC XY: 264905 AN XY: 726280

Gnomad4 AFR exome AF: 0.0684

Gnomad4 AMR exome AF: 0.352

Gnomad4 ASJ exome AF: 0.240

Gnomad4 EAS exome AF: 0.333

Gnomad4 SAS exome AF: 0.462

Gnomad4 FIN exome AF: 0.459

Gnomad4 NFE exome AF: 0.363

Gnomad4 OTH exome AF: 0.337

GnomAD4 genome AF: 0.282 AC: 42828 AN: 152134 Hom.: 7506 Cov.: 33 AF XY: 0.289 AC XY: 21513 AN XY: 74362

Gnomad4 AFR AF: 0.0746

Gnomad4 AMR AF: 0.300

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.333

Gnomad4 SAS AF: 0.465

Gnomad4 FIN AF: 0.454

Gnomad4 NFE AF: 0.364

Gnomad4 OTH AF: 0.264

Alfa AF: 0.342 Hom.: 4912

Bravo AF: 0.255

TwinsUK AF: 0.356 AC: 1321

ALSPAC AF: 0.350 AC: 1350

ESP6500AA AF: 0.0844 AC: 372

ESP6500EA AF: 0.351 AC: 3018

ExAC AF: 0.348 AC: 42301

Asia WGS AF: 0.357 AC: 1242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.066	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.86	D
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-0.95	T
MutationTaster	Benign	1.0	P
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.022
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.093	T
Polyphen		1.0	D
Vest4		0.055
MPC		0.89
ClinPred		0.027	T
GERP RS		1.0
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.0
Varity_R		0.064
gMVP		0.14

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

Publications

LitVar

Other links and lift over

dbSNP: rs886090; hg19: chr9-136199503; COSMIC: COSV64395186;