Variant 17-7482285-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001102614.2(SLC35G6):c.301C>G(p.Arg101Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,613,934 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

SLC35G6
NM_001102614.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.64

Variant links:

Genes affected

SLC35G6 (HGNC:31351): (solute carrier family 35 member G6) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC35G6 links:

ZBTB4 (HGNC:23847): (zinc finger and BTB domain containing 4) Enables several functions, including DNA-binding transcription repressor activity, RNA polymerase II-specific; methyl-CpNpG binding activity; and sequence-specific DNA binding activity. Involved in cellular response to DNA damage stimulus and negative regulation of transcription by RNA polymerase II. Located in cytosol and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

ZBTB4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SLC35G6	NM_001102614.2 linkuse as main transcript	c.301C>G	p.Arg101Gly	missense_variant	2/2	ENST00000412468.4
SLC35G6	XM_047436533.1 linkuse as main transcript	c.307C>G	p.Arg103Gly	missense_variant	2/2
ZBTB4	NM_020899.4 linkuse as main transcript	c.-81+1719G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC35G6	ENST00000412468.4 linkuse as main transcript	c.301C>G	p.Arg101Gly	missense_variant	2/2	1	NM_001102614.2	P1
ZBTB4	ENST00000311403.4 linkuse as main transcript	c.-81+1719G>C		intron_variant		1		P1

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251182

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461672

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000118

AC:

AN:

152262

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.000338

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.0000869

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

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 19, 2023

The c.301C>G (p.R101G) alteration is located in exon 2 (coding exon 2) of the SLC35G6 gene. This alteration results from a C to G substitution at nucleotide position 301, causing the arginine (R) at amino acid position 101 to be replaced by a glycine (G). 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

0.15

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.10

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.050

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.90

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.71

MetaSVM

Benign

-0.81

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-3.7

REVEL

Uncertain

0.30

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.72

MVP

0.48

MPC

1.2

ClinPred

0.62

GERP RS

4.2

Varity_R

0.43

gMVP

0.67

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