7-2432854-A-G

Position:

• chr7-2432854-A-G

Variant summary

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

The NM_018641.5(CHST12):​c.215A>G​(p.Lys72Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,512 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K72N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CHST12 NM_018641.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.384

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=0.08244592).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHST12	NM_018641.5	c.215A>G	p.Lys72Arg	missense_variant	2/2	ENST00000618655.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHST12	ENST00000618655.2	c.215A>G	p.Lys72Arg	missense_variant	2/2	1	NM_018641.5	P1
CHST12	ENST00000258711.7	c.215A>G	p.Lys72Arg	missense_variant	2/2	1		P1
CHST12	ENST00000432336.1	c.215A>G	p.Lys72Arg	missense_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461512 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727086

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	5.5
DANN	Benign	0.93
DEOGEN2	Benign	0.0045	T;T;.
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.71	T;.;T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.082	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;L;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.28	T
Sift4G	Benign	0.26	T;T;T
Polyphen		0.094	B;B;.
Vest4		0.051
MutPred		0.19		Loss of ubiquitination at K72 (P = 0.0074);Loss of ubiquitination at K72 (P = 0.0074);Loss of ubiquitination at K72 (P = 0.0074);
MVP		0.78
MPC		0.42
ClinPred		0.088	T
GERP RS		-0.48
Varity_R		0.033
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr7-2472489;