17-7482232-T-C

Variant names:

• chr17-7482232-T-C
• rs778137794
• NM_001102614.2:c.248T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001102614.2(SLC35G6):​c.248T>C​(p.Ile83Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000725 in 1,613,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000076 (0 hom.)
• Consequence: SLC35G6 NM_001102614.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.85
• Publications: 0 publications found

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]

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16731966).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001102614.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35G6	NM_001102614.2	MANE Select	c.248T>C	p.Ile83Thr	missense	Exon 2 of 2	NP_001096084.1	P0C7Q6
	ZBTB4	NM_020899.4		c.-81+1772A>G		intron	N/A	NP_065950.2	Q9P1Z0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35G6	ENST00000412468.4	TSL:1 MANE Select	c.248T>C	p.Ile83Thr	missense	Exon 2 of 2	ENSP00000396523.2	P0C7Q6
	ZBTB4	ENST00000311403.4	TSL:1	c.-81+1772A>G		intron	N/A	ENSP00000307858.4	Q9P1Z0

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152182 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

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: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 251186 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000441

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000759 AC: 111 AN: 1461674 Hom.: 0 Cov.: 74 AF XY: 0.0000660 AC XY: 48 AN XY: 727146

African (AFR) AF: 0.0000299 AC: 1 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000935 AC: 104 AN: 1111844

Other (OTH) AF: 0.0000828 AC: 5 AN: 60378

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152182 Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4 AN XY: 74348

African (AFR) AF: 0.0000241 AC: 1 AN: 41448

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000154 Hom.: 0

Bravo AF: 0.0000491

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.000164

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.0096	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.074
FATHMM_MKL	Benign	0.70	D
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.4	L
PhyloP100		3.9
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.089
Sift	Benign	0.043	D
Sift4G	Uncertain	0.023	D
Polyphen		0.28	B
Vest4		0.40
MVP		0.25
MPC		0.74
ClinPred		0.22	T
GERP RS		4.3
Varity_R		0.070
gMVP		0.31
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs778137794; hg19: chr17-7385551;