NM_001102614.2:c.496A>T

Variant names:

• chr17-7482480-A-T
• NM_001102614.2:c.496A>T

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.496A>T​(p.Ile166Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC35G6 NM_001102614.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.54
• 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=0.15891191).

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.496A>T	p.Ile166Phe	missense	Exon 2 of 2	NP_001096084.1	P0C7Q6
	ZBTB4	NM_020899.4		c.-81+1524T>A		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.496A>T	p.Ile166Phe	missense	Exon 2 of 2	ENSP00000396523.2	P0C7Q6
	ZBTB4	ENST00000311403.4	TSL:1	c.-81+1524T>A		intron	N/A	ENSP00000307858.4	Q9P1Z0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 117

GnomAD4 genome Cov.: 32

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	0.12
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.0069	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.57	D
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.5
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.039
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.036	D
Polyphen		0.52	P
Vest4		0.19
MutPred		0.29		Loss of glycosylation at S165 (P = 0.12)
MVP		0.19
MPC		0.90
ClinPred		0.47	T
GERP RS		2.8
Varity_R		0.12
gMVP		0.31

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

hg19: chr17-7385799;