6-44254922-C-A

Variant names:

• chr6-44254922-C-A
• rs747564361
• NM_178148.4:c.1083G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_178148.4(SLC35B2):​c.1083G>T​(p.Gln361His) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC35B2 NM_178148.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• Publications: 0 publications found

Genes affected

SLC35B2 (HGNC:16872): (solute carrier family 35 member B2) Sulfotransferases (e.g., SULT4A1; MIM 608359) use an activated form of sulfate, 3-prime-phosphoadenosine 5-prime-phosphosulfate (PAPS), as a common sulfate donor for sulfation of glycoproteins, proteoglycans, and glycolipids in the endoplasmic reticulum and Golgi apparatus. SLC35B2 is located in the microsomal membrane and transports PAPS from the cytosol, where it is synthesized, into the Golgi lumen (Kamiyama et al., 2003 [PubMed 12716889]).[supplied by OMIM, Mar 2008]

SLC35B2 Gene-Disease associations (from GenCC):

• leukodystrophy, hypomyelinating, 26, with chondrodysplasia

  Inheritance: AR Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38415402).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178148.4. 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
	SLC35B2	NM_178148.4	MANE Select	c.1083G>T	p.Gln361His	missense	Exon 4 of 4	NP_835361.1	Q8TB61-1
	SLC35B2	NM_001286509.2		c.1068G>T	p.Gln356His	missense	Exon 4 of 4	NP_001273438.1
	SLC35B2	NM_001286510.2		c.1068G>T	p.Gln356His	missense	Exon 4 of 4	NP_001273439.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35B2	ENST00000393812.4	TSL:1 MANE Select	c.1083G>T	p.Gln361His	missense	Exon 4 of 4	ENSP00000377401.3	Q8TB61-1
	SLC35B2	ENST00000615337.4	TSL:4	c.936G>T	p.Gln312His	missense	Exon 4 of 4	ENSP00000480681.1	Q8TB61-3
	SLC35B2	ENST00000538577.5	TSL:2	c.804G>T	p.Gln268His	missense	Exon 3 of 3	ENSP00000443845.1	Q8TB61-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.056	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.3
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.057
Sift	Benign	0.093	T
Sift4G	Benign	0.14	T
Polyphen		0.060	B
Vest4		0.36
MutPred		0.44		Gain of helix (P = 0.132)
MVP		0.11
MPC		0.12
ClinPred		0.62	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.32
gMVP		0.65
Mutation Taster		=63/37	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: rs747564361; hg19: chr6-44222659;