chr6-8417461-T-G

Position:

• chr6-8417461-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001370476.2(SLC35B3):​c.814A>C​(p.Ile272Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC35B3 NM_001370476.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.02

Genes affected

SLC35B3 (HGNC:21601): (solute carrier family 35 member B3) This gene is a member of the solute carrier family. The encoded protein is involved in the transport of 3-prime phosphoadenosine 5-prime phosphosulfate (PAPS) from the nucleus or the cytosol to the Golgi lumen. This gene has been reported to be expressed preferentially in the human colon tissues. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

SLC35B3 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22150111).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC35B3	NM_001370476.2	c.814A>C	p.Ile272Leu	missense_variant	8/11	ENST00000644923.2	NP_001357405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC35B3	ENST00000644923.2	c.814A>C	p.Ile272Leu	missense_variant	8/11		NM_001370476.2	ENSP00000496368.1
SLC35B3	ENST00000710437.1	c.718A>C	p.Ile240Leu	missense_variant	7/10			ENSP00000518269.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

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

Nov 14, 2024

The c.814A>C (p.I272L) alteration is located in exon 8 (coding exon 7) of the SLC35B3 gene. This alteration results from a A to C substitution at nucleotide position 814, causing the isoleucine (I) at amino acid position 272 to be replaced by a leucine (L). 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	0.16
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	20
DANN	Benign	0.79
DEOGEN2	Benign	0.018	.;T;T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.13
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D;.;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.17	.;N;N
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.040	.;N;.
REVEL	Benign	0.19
Sift	Benign	1.0	.;T;.
Sift4G	Benign	1.0	.;T;.
Polyphen		0.074	.;B;B
Vest4		0.77
MutPred		0.45		.;Gain of catalytic residue at I272 (P = 0.0577);Gain of catalytic residue at I272 (P = 0.0577);
MVP		0.21
MPC		0.11
ClinPred		0.76	D
GERP RS		5.7
Varity_R		0.22
gMVP		0.62

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

Other links and lift over

dbSNP: rs778543593; hg19: chr6-8417694;