16-75529562-C-T

Variant names:

• chr16-75529562-C-T
• NM_024533.5:c.823G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024533.5(CHST5):​c.823G>A​(p.Ala275Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,456,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign 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. A275S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CHST5 NM_024533.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13494277).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST5	NM_024533.5	c.823G>A	p.Ala275Thr	missense_variant	Exon 4 of 4	ENST00000336257.8	NP_078809.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHST5	ENST00000336257.8	c.823G>A	p.Ala275Thr	missense_variant	Exon 4 of 4	1	NM_024533.5	ENSP00000338783.3
ENSG00000260092	ENST00000460606.1	n.*922G>A		non_coding_transcript_exon_variant	Exon 5 of 5	1		ENSP00000457544.1
ENSG00000260092	ENST00000460606.1	n.*922G>A		3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000457544.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1456858 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 724860

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: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.82	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.5	L
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	0.060	N
REVEL	Benign	0.13
Sift	Benign	0.33	T
Sift4G	Benign	0.28	T
Polyphen		0.075	B
Vest4		0.071
MutPred		0.42		Gain of phosphorylation at A275 (P = 0.041);
MVP		0.82
MPC		0.59
ClinPred		0.17	T
GERP RS		1.7
Varity_R		0.085
gMVP		0.86

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-75563460;