NM_004854.5:c.998G>C

Variant names:

• chr2-100393318-C-G
• rs756945972
• NM_004854.5:c.998G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_004854.5(CHST10):​c.998G>C​(p.Arg333Pro) variant causes a missense change. 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. R333Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHST10 NM_004854.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.04
• Publications: 0 publications found

Genes affected

CHST10 (HGNC:19650): (carbohydrate sulfotransferase 10) This protein encoded by this gene transfers sulfate to the C-3 hydroxyl of terminal glucuronic acid of protein- and lipid-linked oligosaccharides. This protein was first identified as a sulfotransferase that acts on the human natural killer-1 (HNK-1) glycan; HNK-1 is a carbohydrate involved in neurodevelopment and synaptic plasticity.[provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.886

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004854.5. 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
	CHST10	NM_004854.5	MANE Select	c.998G>C	p.Arg333Pro	missense	Exon 7 of 7	NP_004845.1	O43529

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST10	ENST00000264249.8	TSL:1 MANE Select	c.998G>C	p.Arg333Pro	missense	Exon 7 of 7	ENSP00000264249.3	O43529
	CHST10	ENST00000409701.5	TSL:1	c.998G>C	p.Arg333Pro	missense	Exon 7 of 7	ENSP00000387309.1	O43529
	CHST10	ENST00000972083.1		c.1061G>C	p.Arg354Pro	missense	Exon 8 of 8	ENSP00000642142.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.30
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.79	D
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Uncertain	0.26	D
MutationAssessor	Pathogenic	3.1	M
PhyloP100		5.0
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.8	D
REVEL	Pathogenic	0.66
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.74
MutPred		0.72		Loss of MoRF binding (P = 9e-04)
MVP		0.97
MPC		1.4
ClinPred		0.98	D
GERP RS		5.9
Varity_R		0.97
gMVP		0.94
Mutation Taster		=8/92	disease causing

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: rs756945972; hg19: chr2-101009780;