Genetic Variant CHST5:p.Thr318Arg (chr16-75529432-G-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_024533.5(CHST5):c.953C>G(p.Thr318Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000049 in 1,612,928 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. T318M) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

CHST5
NM_024533.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.32

Variant links:

Genes affected

CHST5 (HGNC:1973): (carbohydrate sulfotransferase 5) The protein encoded by this gene belongs to the Gal/GalNAc/GlcNAc 6-O-sulfotransferase (GST) family, members of which catalyze the transfer of sulfate to position 6 of galactose (Gal), N-acetylgalactosamine (GalNAc), or N-acetylglucosamine (GlcNAc) residues within proteoglycans, and sulfation of O-linked sugars of mucin-type acceptors. Carbohydrate sulfation plays a critical role in many biologic processes. This gene is predominantly expressed in colon and small intestine. [provided by RefSeq, Aug 2011]

CHST5 links:

ENSG00000260092 (HGNC:):

ENSG00000260092 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.787

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST5	NM_024533.5 link	c.953C>G	p.Thr318Arg	missense_variant	Exon 4 of 4	ENST00000336257.8	NP_078809.2	Q9GZS9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CHST5	ENST00000336257.8 link	c.953C>G	p.Thr318Arg	missense_variant	Exon 4 of 4	1	NM_024533.5	ENSP00000338783.3	Q9GZS9-1
ENSG00000260092	ENST00000460606.1 link	n.*1052C>G		non_coding_transcript_exon_variant	Exon 5 of 5	1		ENSP00000457544.1	H3BUA1
ENSG00000260092	ENST00000460606.1 link	n.*1052C>G		3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000457544.1	H3BUA1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152182

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:

0.00

Gnomad FIN

AF:

0.000848

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000363

AC:

AN:

248110

Hom.:

AF XY:

0.0000371

AC XY:

AN XY:

134652

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:

0.00

Gnomad FIN exome

AF:

0.000279

Gnomad NFE exome

AF:

0.00000901

Gnomad OTH exome

AF:

0.000329

GnomAD4 exome

AF:

0.0000466

AC:

AN:

1460628

Hom.:

Cov.:

AF XY:

0.0000468

AC XY:

AN XY:

726664

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:

0.00

Gnomad4 FIN exome

AF:

0.000955

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000722

AC:

AN:

152300

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74454

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:

0.00

Gnomad4 FIN

AF:

0.000848

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000135

Hom.:

2642

ExAC

AF:

0.0000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Uncertain

0.016

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.69

Eigen

Uncertain

0.31

Eigen_PC

Benign

0.16

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.73

M_CAP

Benign

0.019

MetaRNN

Pathogenic

0.79

MetaSVM

Benign

-0.74

MutationAssessor

Uncertain

2.9

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.26

Sift

Benign

0.040

Sift4G

Benign

0.31

Polyphen

1.0

Vest4

0.56

MutPred

0.50

Loss of helix (P = 0.2271);

MVP

0.52

MPC

1.5

ClinPred

0.87

GERP RS

2.8

Varity_R

0.82

gMVP

0.91

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over