chr17-7482286-G-C

Variant names:

• chr17-7482286-G-C
• rs751688186
• NM_001102614.2:c.302G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001102614.2(SLC35G6):​c.302G>C​(p.Arg101Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R101Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC35G6 NM_001102614.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.26
• Publications: 1 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.809

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.302G>C	p.Arg101Pro	missense	Exon 2 of 2	NP_001096084.1	P0C7Q6
	ZBTB4	NM_020899.4		c.-81+1718C>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.302G>C	p.Arg101Pro	missense	Exon 2 of 2	ENSP00000396523.2	P0C7Q6
	ZBTB4	ENST00000311403.4	TSL:1	c.-81+1718C>G		intron	N/A	ENSP00000307858.4	Q9P1Z0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 90

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.051	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Uncertain	0.089	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		8.3
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.79
MutPred		0.64		Loss of helix (P = 0.0093)
MVP		0.49
MPC		1.3
ClinPred		0.99	D
GERP RS		4.2
Varity_R		0.66
gMVP		0.83

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

Other links and lift over

dbSNP: rs751688186; hg19: chr17-7385605;