2-100393748-C-A

Variant names:

• chr2-100393748-C-A
• rs368455898
• NM_004854.5:c.568G>T

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PM1 PM2 PP3_Strong

The NM_004854.5(CHST10):​c.568G>T​(p.Asp190Tyr) 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. D190H) 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: 7.71
• Publications: 2 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: Likely_pathogenic. The variant received 8 ACMG points.

• PM1: In a mutagenesis_site Induces a mild reduction in enzyme activity. (size 0) in uniprot entity CHSTA_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.953

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.568G>T	p.Asp190Tyr	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.568G>T	p.Asp190Tyr	missense	Exon 7 of 7	ENSP00000264249.3	O43529
	CHST10	ENST00000409701.5	TSL:1	c.568G>T	p.Asp190Tyr	missense	Exon 7 of 7	ENSP00000387309.1	O43529
	CHST10	ENST00000972083.1		c.631G>T	p.Asp211Tyr	missense	Exon 8 of 8	ENSP00000642142.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 247782 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.81	D
Eigen	Pathogenic	0.95
Eigen_PC	Pathogenic	0.93
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.025	T
MetaRNN	Pathogenic	0.95	D
MetaSVM	Uncertain	0.39	D
MutationAssessor	Pathogenic	3.0	M
PhyloP100		7.7
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-5.1	D
REVEL	Uncertain	0.60
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.91
MutPred		0.83		Gain of MoRF binding (P = 0.0534)
MVP		0.68
MPC		1.3
ClinPred		1.0	D
GERP RS		6.1
Varity_R		0.91
gMVP		0.92
Mutation Taster		=9/91	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs368455898; hg19: chr2-101010210; COSMIC: COSV51805119; COSMIC: COSV51805119;