16-75529268-C-A

Variant names:

• chr16-75529268-C-A
• rs143129709
• NM_024533.5:c.1117G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024533.5(CHST5):​c.1117G>T​(p.Gly373Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,742 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G373S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CHST5 NM_024533.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.85
• Publications: 0 publications found

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]

ENSG00000260092 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024533.5. 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
	CHST5	NM_024533.5	MANE Select	c.1117G>T	p.Gly373Cys	missense	Exon 4 of 4	NP_078809.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST5	ENST00000336257.8	TSL:1 MANE Select	c.1117G>T	p.Gly373Cys	missense	Exon 4 of 4	ENSP00000338783.3	Q9GZS9-1
	ENSG00000260092	ENST00000460606.1	TSL:1	n.*1216G>T		non_coding_transcript_exon	Exon 5 of 5	ENSP00000457544.1	H3BUA1
	ENSG00000260092	ENST00000460606.1	TSL:1	n.*1216G>T		3_prime_UTR	Exon 5 of 5	ENSP00000457544.1	H3BUA1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460742 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726722

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52516

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111894

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Pathogenic	0.81	D
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.75
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.86	D
M_CAP	Uncertain	0.099	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Uncertain	0.061	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		3.9
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.40
Sift	Benign	0.035	D
Sift4G	Uncertain	0.045	D
Polyphen		1.0	D
Vest4		0.44
MutPred		0.47		Loss of catalytic residue at A372 (P = 0.1376)
MVP		0.85
MPC		1.5
ClinPred		0.94	D
GERP RS		0.81
Varity_R		0.66
gMVP		0.82
Mutation Taster		=96/4	polymorphism

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: rs143129709; hg19: chr16-75563166;