7-2432938-G-C

Position:

• chr7-2432938-G-C

Variant summary

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

The NM_018641.5(CHST12):​c.299G>C​(p.Ser100Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,072 control chromosomes in the GnomAD database, including 1 homozygotes. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (1 hom.)
• Consequence: CHST12 NM_018641.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.713

Genes affected

CHST12 (HGNC:17423): (carbohydrate sulfotransferase 12) The protein encoded by this gene belongs to the sulfotransferase 2 family. It is localized to the golgi membrane, and catalyzes the transfer of sulfate to position 4 of the N-acetylgalactosamine (GalNAc) residue of chondroitin and desulfated dermatan sulfate. Chondroitin sulfate constitutes the predominant proteoglycan present in cartilage, and is distributed on the surfaces of many cells and extracellular matrices. Alternatively spliced transcript variants differing only in their 5' UTRs have been found for this gene. [provided by RefSeq, Aug 2011]

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=0.06978828).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHST12	NM_018641.5	c.299G>C	p.Ser100Thr	missense_variant	2/2	ENST00000618655.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHST12	ENST00000618655.2	c.299G>C	p.Ser100Thr	missense_variant	2/2	1	NM_018641.5	P1
CHST12	ENST00000258711.7	c.299G>C	p.Ser100Thr	missense_variant	2/2	1		P1
CHST12	ENST00000432336.1	c.299G>C	p.Ser100Thr	missense_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460072 Hom.: 1 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 726306

Gnomad4 AFR exome AF: 0.0000299

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 12, 2021

The c.299G>C (p.S100T) alteration is located in exon 2 (coding exon 1) of the CHST12 gene. This alteration results from a G to C substitution at nucleotide position 299, causing the serine (S) at amino acid position 100 to be replaced by a threonine (T). 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	0.083
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	14
DANN	Benign	0.88
DEOGEN2	Benign	0.0039	T;T;.
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.63	T;.;T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.070	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;L;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.39	T
Sift4G	Benign	0.63	T;T;T
Polyphen		0.057	B;B;.
Vest4		0.086
MutPred		0.29		Loss of glycosylation at S100 (P = 0.0565);Loss of glycosylation at S100 (P = 0.0565);Loss of glycosylation at S100 (P = 0.0565);
MVP		0.65
MPC		0.47
ClinPred		0.036	T
GERP RS		1.7
Varity_R		0.030
gMVP		0.17

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: chr7-2472573;