Genetic Variant CHST5:p.Val229Met (chr16-75529700-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_024533.5(CHST5):c.685G>A(p.Val229Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00091 in 1,610,994 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00071 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00093 ( 2 hom. )

Consequence

CHST5
NM_024533.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.52

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST5	NM_024533.5 link	c.685G>A	p.Val229Met	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.685G>A	p.Val229Met	missense_variant	Exon 4 of 4	1	NM_024533.5	ENSP00000338783.3	Q9GZS9-1
ENSG00000260092	ENST00000460606.1 link	n.*784G>A		non_coding_transcript_exon_variant	Exon 5 of 5	1		ENSP00000457544.1	H3BUA1
ENSG00000260092	ENST00000460606.1 link	n.*784G>A		3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000457544.1	H3BUA1

Frequencies

GnomAD3 genomes

AF:

0.000710

AC:

108

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00122

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000438

AC:

106

AN:

242096

Hom.:

AF XY:

0.000417

AC XY:

AN XY:

131804

show subpopulations

Gnomad AFR exome

AF:

0.000195

Gnomad AMR exome

AF:

0.000320

Gnomad ASJ exome

AF:

0.000307

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000800

Gnomad OTH exome

AF:

0.000335

GnomAD4 exome

AF:

0.000931

AC:

1358

AN:

1458728

Hom.:

Cov.:

AF XY:

0.000885

AC XY:

642

AN XY:

725610

show subpopulations

Gnomad4 AFR exome

AF:

0.000180

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.000384

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.0000384

Gnomad4 NFE exome

AF:

0.00112

Gnomad4 OTH exome

AF:

0.00126

GnomAD4 genome

AF:

0.000709

AC:

108

AN:

152266

Hom.:

Cov.:

AF XY:

0.000483

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00122

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000877

Hom.:

Bravo

AF:

0.000665

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000685

AC:

ESP6500EA

AF:

0.000817

AC:

ExAC

AF:

0.000400

AC:

EpiCase

AF:

0.00136

EpiControl

AF:

0.000948

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 20, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.685G>A (p.V229M) alteration is located in exon 3 (coding exon 1) of the CHST5 gene. This alteration results from a G to A substitution at nucleotide position 685, causing the valine (V) at amino acid position 229 to be replaced by a methionine (M). 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

Uncertain

0.46

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.80

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.032

MetaRNN

Uncertain

0.65

MetaSVM

Benign

-0.72

MutationAssessor

Pathogenic

3.2

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-2.9

REVEL

Uncertain

0.37

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.78

MVP

0.58

MPC

1.5

ClinPred

0.19

GERP RS

2.6

Varity_R

0.69

gMVP

0.89

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