Genetic Variant CHST10:p.Pro104Ser (chr2-100398025-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004854.5(CHST10):c.310C>T(p.Pro104Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000619 in 1,614,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

CHST10
NM_004854.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.126

Variant links:

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]

CHST10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06302109).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST10	NM_004854.5 link	c.310C>T	p.Pro104Ser	missense_variant	Exon 5 of 7	ENST00000264249.8	NP_004845.1	O43529

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHST10	ENST00000264249.8 link	c.310C>T	p.Pro104Ser	missense_variant	Exon 5 of 7	1	NM_004854.5	ENSP00000264249.3		O43529

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251474

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135912

show subpopulations

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 SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000656

AC:

AN:

152328

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000247

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.310C>T (p.P104S) alteration is located in exon 5 (coding exon 3) of the CHST10 gene. This alteration results from a C to T substitution at nucleotide position 310, causing the proline (P) at amino acid position 104 to be replaced by a serine (S). 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

0.065

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.53

CADD

Benign

4.0

DANN

Benign

0.67

DEOGEN2

Benign

0.024

T;T;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.79

.;T;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.063

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N;.;.

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.26

N;N;N;N

REVEL

Benign

0.078

Sift

Benign

0.60

T;T;T;T

Sift4G

Benign

0.81

T;T;.;T

Polyphen

0.0

B;B;.;.

Vest4

0.075

MutPred

0.31

Gain of disorder (P = 0.0702);Gain of disorder (P = 0.0702);Gain of disorder (P = 0.0702);Gain of disorder (P = 0.0702);

MVP

0.61

MPC

0.38

ClinPred

0.011

GERP RS

3.9

Varity_R

0.030

gMVP

0.20

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over