Variant 9-133356665-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017503.5(SURF2):c.73C>T(p.Arg25Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0206 in 1,516,852 control chromosomes in the GnomAD database, including 611 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 99 hom., cov: 32)

Exomes 𝑓: 0.021 ( 512 hom. )

Consequence

SURF2
NM_017503.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.20

Variant links:

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]

SURF2 links:

SURF1 (HGNC:):

SURF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015997291).

BP6

Variant 9-133356665-C-T is Benign according to our data. Variant chr9-133356665-C-T is described in ClinVar as [Benign]. Clinvar id is 1292593.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-133356665-C-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SURF2	NM_017503.5 linkuse as main transcript	c.73C>T	p.Arg25Cys	missense_variant	1/6	ENST00000371964.5	NP_059973.4	Q15527
SURF2	NM_001278928.2 linkuse as main transcript	c.73C>T	p.Arg25Cys	missense_variant	1/6		NP_001265857.1	Q15527

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SURF2	ENST00000371964.5 linkuse as main transcript	c.73C>T	p.Arg25Cys	missense_variant	1/6	1	NM_017503.5	ENSP00000361032.4	Q15527
SURF1	ENST00000463965.1 linkuse as main transcript	n.12G>A		non_coding_transcript_exon_variant	1/2	3
SURF2	ENST00000495524.5 linkuse as main transcript	n.88C>T		non_coding_transcript_exon_variant	1/4	5

Frequencies

GnomAD3 genomes

AF:

0.0204

AC:

3105

AN:

151938

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00491

Gnomad AMI

AF:

0.0296

Gnomad AMR

AF:

0.0826

Gnomad ASJ

AF:

0.0329

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.0433

Gnomad FIN

AF:

0.0129

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0160

Gnomad OTH

AF:

0.0279

GnomAD3 exomes

AF:

0.0440

AC:

4894

AN:

111340

Hom.:

217

AF XY:

0.0396

AC XY:

2451

AN XY:

61926

show subpopulations

Gnomad AFR exome

AF:

0.00569

Gnomad AMR exome

AF:

0.119

Gnomad ASJ exome

AF:

0.0380

Gnomad EAS exome

AF:

0.000501

Gnomad SAS exome

AF:

0.0511

Gnomad FIN exome

AF:

0.0113

Gnomad NFE exome

AF:

0.0190

Gnomad OTH exome

AF:

0.0333

GnomAD4 exome

AF:

0.0206

AC:

28147

AN:

1364806

Hom.:

512

Cov.:

AF XY:

0.0211

AC XY:

14229

AN XY:

673136

show subpopulations

Gnomad4 AFR exome

AF:

0.00353

Gnomad4 AMR exome

AF:

0.108

Gnomad4 ASJ exome

AF:

0.0363

Gnomad4 EAS exome

AF:

0.000296

Gnomad4 SAS exome

AF:

0.0473

Gnomad4 FIN exome

AF:

0.0114

Gnomad4 NFE exome

AF:

0.0170

Gnomad4 OTH exome

AF:

0.0212

GnomAD4 genome

AF:

0.0205

AC:

3114

AN:

152046

Hom.:

Cov.:

AF XY:

0.0222

AC XY:

1651

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.00492

Gnomad4 AMR

AF:

0.0831

Gnomad4 ASJ

AF:

0.0329

Gnomad4 EAS

AF:

0.000388

Gnomad4 SAS

AF:

0.0433

Gnomad4 FIN

AF:

0.0129

Gnomad4 NFE

AF:

0.0160

Gnomad4 OTH

AF:

0.0276

Alfa

AF:

0.0184

Hom.:

Bravo

AF:

0.0261

ESP6500AA

AF:

0.00286

AC:

ESP6500EA

AF:

0.0120

AC:

ExAC

AF:

0.0164

AC:

1473

Asia WGS

AF:

0.0190

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 28, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.70

CADD

Benign

3.9

DANN

Benign

0.93

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0060

MetaRNN

Benign

0.0016

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.9

REVEL

Benign

0.017

Sift

Benign

0.090

Sift4G

Benign

0.083

Vest4

0.049

MPC

0.079

ClinPred

0.0051

GERP RS

-5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

gMVP

0.34

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over