Variant 9-133332570-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006753.6(SURF6):c.584C>T(p.Pro195Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000392 in 1,608,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

SURF6
NM_006753.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.880

Variant links:

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]

SURF6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.027011812).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SURF6	NM_006753.6 linkuse as main transcript	c.584C>T	p.Pro195Leu	missense_variant	4/5	ENST00000372022.6
SURF6	NM_001278942.2 linkuse as main transcript	c.583C>T	p.Arg195Cys	missense_variant	4/5
SURF6	NR_103874.2 linkuse as main transcript	n.587C>T		non_coding_transcript_exon_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SURF6	ENST00000372022.6 linkuse as main transcript	c.584C>T	p.Pro195Leu	missense_variant	4/5	1	NM_006753.6	P1
SURF6	ENST00000468290.1 linkuse as main transcript	n.370C>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000285

AC:

AN:

245466

Hom.:

AF XY:

0.0000300

AC XY:

AN XY:

133412

show subpopulations

Gnomad AFR exome

AF:

0.000126

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000889

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000343

AC:

AN:

1456424

Hom.:

Cov.:

AF XY:

0.0000359

AC XY:

AN XY:

724810

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000225

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000853

AC:

AN:

152352

Hom.:

Cov.:

AF XY:

0.0000805

AC XY:

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.000216

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000106

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 20, 2024

The c.584C>T (p.P195L) alteration is located in exon 4 (coding exon 4) of the SURF6 gene. This alteration results from a C to T substitution at nucleotide position 584, causing the proline (P) at amino acid position 195 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.12

DANN

Benign

0.65

DEOGEN2

Benign

0.0052

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.094

LIST_S2

Benign

0.43

M_CAP

Benign

0.0040

MetaRNN

Benign

0.027

MetaSVM

Benign

-0.96

MutationTaster

Benign

1.0

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.2

REVEL

Benign

0.0030

Sift

Benign

0.26

Sift4G

Benign

0.29

Polyphen

0.0030

Vest4

0.12

MVP

0.099

MPC

0.45

ClinPred

0.029

GERP RS

-3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.031

gMVP

0.051

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