Genetic Variant SLC35G6:c.4-133G>C (chr17-7481855-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001102614.2(SLC35G6):c.4-133G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 1,310,276 control chromosomes in the GnomAD database, including 370,528 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 0.73 ( 41268 hom., cov: 31)

Exomes 𝑓: 0.75 ( 329260 hom. )

Consequence

SLC35G6
NM_001102614.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.51

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SLC35G6	NM_001102614.2 link	c.4-133G>C	intron_variant	Intron 1 of 1	ENST00000412468.4	NP_001096084.1	P0C7Q6
ZBTB4	NM_020899.4 link	c.-81+2149C>G	intron_variant	Intron 1 of 3		NP_065950.2	Q9P1Z0B3KVD4
SLC35G6	XM_047436533.1 link	c.10-133G>C	intron_variant	Intron 1 of 1		XP_047292489.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC35G6	ENST00000412468.4 link	c.4-133G>C		intron_variant	Intron 1 of 1	1	NM_001102614.2	ENSP00000396523.2		P0C7Q6
ZBTB4	ENST00000311403.4 link	c.-81+2149C>G		intron_variant	Intron 1 of 3	1		ENSP00000307858.4		Q9P1Z0

Frequencies

GnomAD3 genomes

AF:

0.731

AC:

111098

AN:

151934

Hom.:

41237

Cov.:

show subpopulations

Gnomad AFR

AF:

0.614

Gnomad AMI

AF:

0.711

Gnomad AMR

AF:

0.809

Gnomad ASJ

AF:

0.729

Gnomad EAS

AF:

0.911

Gnomad SAS

AF:

0.708

Gnomad FIN

AF:

0.832

Gnomad MID

AF:

0.718

Gnomad NFE

AF:

0.757

Gnomad OTH

AF:

0.737

GnomAD4 exome

AF:

0.753

AC:

871705

AN:

1158224

Hom.:

329260

AF XY:

0.752

AC XY:

427092

AN XY:

567814

show subpopulations

African (AFR)

AF:

0.611

AC:

15683

AN:

25654

American (AMR)

AF:

0.836

AC:

16708

AN:

19980

Ashkenazi Jewish (ASJ)

AF:

0.725

AC:

13085

AN:

18036

East Asian (EAS)

AF:

0.882

AC:

30624

AN:

34740

South Asian (SAS)

AF:

0.712

AC:

42940

AN:

60282

European-Finnish (FIN)

AF:

0.818

AC:

33024

AN:

40370

Middle Eastern (MID)

AF:

0.692

AC:

3100

AN:

4478

European-Non Finnish (NFE)

AF:

0.751

AC:

679970

AN:

905520

Other (OTH)

AF:

0.744

AC:

36571

AN:

49164

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

11010

22019

33029

44038

55048

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.731

AC:

111172

AN:

152052

Hom.:

41268

Cov.:

AF XY:

0.737

AC XY:

54783

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.614

AC:

25441

AN:

41414

American (AMR)

AF:

0.809

AC:

12360

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.729

AC:

2528

AN:

3468

East Asian (EAS)

AF:

0.911

AC:

4708

AN:

5168

South Asian (SAS)

AF:

0.709

AC:

3414

AN:

4818

European-Finnish (FIN)

AF:

0.832

AC:

8824

AN:

10604

Middle Eastern (MID)

AF:

0.714

AC:

210

AN:

294

European-Non Finnish (NFE)

AF:

0.757

AC:

51478

AN:

67984

Other (OTH)

AF:

0.738

AC:

1561

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1464

2927

4391

5854

7318

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.686

Hom.:

2152

Bravo

AF:

0.724

Asia WGS

AF:

0.813

AC:

2827

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.9

(source)

DANN

Benign

0.58

PhyloP100

-1.5

PromoterAI

-0.0060

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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 for variant 17:7481855 G>C . It may be empty.

chr17-7481855-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over