12-104757414-G-C

Variant names:

• chr12-104757414-G-C
• rs148230565
• NM_018413.6:c.670G>C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_018413.6(CHST11):​c.670G>C​(p.Ala224Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00371 in 1,613,938 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0038 (17 hom.)
• Consequence: CHST11 NM_018413.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 6.69

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007696897).
• BP6: Variant 12-104757414-G-C is Benign according to our data. Variant chr12-104757414-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2643254.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST11	NM_018413.6	c.670G>C	p.Ala224Pro	missense_variant	Exon 3 of 3	ENST00000303694.6	NP_060883.1
CHST11	NM_001173982.2	c.655G>C	p.Ala219Pro	missense_variant	Exon 3 of 3		NP_001167453.1
CHST11	XM_047428914.1	c.433G>C	p.Ala145Pro	missense_variant	Exon 2 of 2		XP_047284870.1
CHST11	XM_047428915.1	c.433G>C	p.Ala145Pro	missense_variant	Exon 2 of 2		XP_047284871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHST11	ENST00000303694.6	c.670G>C	p.Ala224Pro	missense_variant	Exon 3 of 3	1	NM_018413.6	ENSP00000305725.5
CHST11	ENST00000549260.5	c.655G>C	p.Ala219Pro	missense_variant	Exon 3 of 3	1		ENSP00000450004.1

Frequencies

GnomAD3 genomes AF: 0.00271 AC: 411 AN: 151928 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000750

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00435

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00413

Gnomad OTH AF: 0.00480

GnomAD3 exomes AF: 0.00261 AC: 656 AN: 251464 Hom.: 1 AF XY: 0.00255 AC XY: 347 AN XY: 135916

Gnomad AFR exome AF: 0.000800

Gnomad AMR exome AF: 0.00176

Gnomad ASJ exome AF: 0.000496

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000359

Gnomad FIN exome AF: 0.00439

Gnomad NFE exome AF: 0.00396

Gnomad OTH exome AF: 0.00342

GnomAD4 exome AF: 0.00381 AC: 5571 AN: 1461892 Hom.: 17 Cov.: 31 AF XY: 0.00366 AC XY: 2659 AN XY: 727246

Gnomad4 AFR exome AF: 0.000747

Gnomad4 AMR exome AF: 0.00181

Gnomad4 ASJ exome AF: 0.000191

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000301

Gnomad4 FIN exome AF: 0.00440

Gnomad4 NFE exome AF: 0.00449

Gnomad4 OTH exome AF: 0.00328

GnomAD4 genome AF: 0.00270 AC: 411 AN: 152046 Hom.: 2 Cov.: 32 AF XY: 0.00256 AC XY: 190 AN XY: 74300

Gnomad4 AFR AF: 0.000747

Gnomad4 AMR AF: 0.00236

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000416

Gnomad4 FIN AF: 0.00435

Gnomad4 NFE AF: 0.00413

Gnomad4 OTH AF: 0.00475

Alfa AF: 0.00376 Hom.: 1

Bravo AF: 0.00266

TwinsUK AF: 0.00378 AC: 14

ALSPAC AF: 0.00337 AC: 13

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00465 AC: 40

ExAC AF: 0.00255 AC: 310

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00431

EpiControl AF: 0.00356

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CHST11: BS2 -

CHST11-related disorder Benign:1

Apr 19, 2021

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Uncertain	0.010
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.23	.;T
Eigen	Benign	-0.052
Eigen_PC	Benign	0.19
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.0077	T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	-0.11	.;N
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.3	N;N
REVEL	Uncertain	0.33
Sift	Benign	0.65	T;T
Sift4G	Benign	0.47	T;T
Polyphen		0.028	B;B
Vest4		0.25
MVP		0.70
MPC		1.1
ClinPred		0.022	T
GERP RS		5.4
Varity_R		0.37
gMVP		0.82

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: rs148230565; hg19: chr12-105151192;