17-7482316-A-C

Variant summary

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

The NM_001102614.2(SLC35G6):c.332A>C(p.Asn111Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC35G6 NM_001102614.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.95

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

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	UniProt
SLC35G6	NM_001102614.2	c.332A>C	p.Asn111Thr	missense_variant	2/2	ENST00000412468.4
SLC35G6	XM_047436533.1	c.338A>C	p.Asn113Thr	missense_variant	2/2
ZBTB4	NM_020899.4	c.-81+1688T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC35G6	ENST00000412468.4	c.332A>C	p.Asn111Thr	missense_variant	2/2	1	NM_001102614.2	P1
ZBTB4	ENST00000311403.4	c.-81+1688T>G		intron_variant		1		P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 102

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 27, 2022

The c.332A>C (p.N111T) alteration is located in exon 2 (coding exon 2) of the SLC35G6 gene. This alteration results from a A to C substitution at nucleotide position 332, causing the asparagine (N) at amino acid position 111 to be replaced by a threonine (T). 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	0.17
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
Cadd	Benign	17
Dann	Uncertain	0.98
DEOGEN2	Benign	0.068	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.85	D
M_CAP	Benign	0.077	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.14
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.025	D
Polyphen		0.89	P
Vest4		0.69
MutPred		0.61		Gain of sheet (P = 0.0827);
MVP		0.16
MPC		0.83
ClinPred		0.54	D
GERP RS		3.0
Varity_R		0.14
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-7385635;