NM_018413.6:c.29G>C

Variant names:

• chr12-104457440-G-C
• rs374980790
• NM_018413.6:c.29G>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_018413.6(CHST11):​c.29G>C​(p.Arg10Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: CHST11 NM_018413.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.66

Genes affected

CHST11 (HGNC:17422): (carbohydrate sulfotransferase 11) 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. Chondroitin sulfate constitutes the predominant proteoglycan present in cartilage, and is distributed on the surfaces of many cells and extracellular matrices. A chromosomal translocation involving this gene and IgH, t(12;14)(q23;q32), has been reported in a patient with B-cell chronic lymphocytic leukemia. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.762

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST11	NM_018413.6	c.29G>C	p.Arg10Thr	missense_variant	Exon 1 of 3	ENST00000303694.6	NP_060883.1
CHST11	NM_001173982.2	c.29G>C	p.Arg10Thr	missense_variant	Exon 1 of 3		NP_001167453.1
CHST11	XM_047428914.1	c.-123G>C		5_prime_UTR_variant	Exon 1 of 2		XP_047284870.1
CHST11	XM_047428915.1	c.-108G>C		5_prime_UTR_variant	Exon 1 of 2		XP_047284871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHST11	ENST00000303694.6	c.29G>C	p.Arg10Thr	missense_variant	Exon 1 of 3	1	NM_018413.6	ENSP00000305725.5
CHST11	ENST00000549260.5	c.29G>C	p.Arg10Thr	missense_variant	Exon 1 of 3	1		ENSP00000450004.1
CHST11	ENST00000547956.1	c.29G>C	p.Arg10Thr	missense_variant	Exon 1 of 2	2		ENSP00000449093.1
CHST11	ENST00000546689.1	c.29G>C	p.Arg10Thr	missense_variant	Exon 1 of 2	2		ENSP00000448678.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251322 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135854

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461756 Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4 AN XY: 727196

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: 0.0000126

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	29
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T;.;T;T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.89	D;D;D;D
M_CAP	Benign	0.070	D
MetaRNN	Pathogenic	0.76	D;D;D;D
MetaSVM	Benign	-0.32	T
MutationAssessor	Benign	1.6	.;L;L;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.8	D;N;N;D
REVEL	Uncertain	0.48
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0, 0.91	.;D;P;.
Vest4		0.91
MutPred		0.43		Loss of MoRF binding (P = 0.0361);Loss of MoRF binding (P = 0.0361);Loss of MoRF binding (P = 0.0361);Loss of MoRF binding (P = 0.0361);
MVP		0.94
MPC		1.8
ClinPred		0.99	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		3.7
Varity_R		0.50
gMVP		0.66

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

Other links and lift over

dbSNP: rs374980790; hg19: chr12-104851218;