12-104757221-CAACCTGAAGACCCTG-C

Position:

• chr12-104757221-CAACCTGAAGACCCTG-C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM4 PP3

The NM_018413.6(CHST11):​c.482_496delTGAAGACCCTGAACC​(p.Leu161_Asn165del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHST11 NM_018413.6 disruptive_inframe_deletion
• Clinical Significance: Conflicting classifications of pathogenicity no assertion criteria provided P:1 U:1
• Conservation: PhyloP100: 9.32

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 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_018413.6.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHST11	NM_018413.6	c.482_496delTGAAGACCCTGAACC	p.Leu161_Asn165del	disruptive_inframe_deletion	3/3	ENST00000303694.6	NP_060883.1
CHST11	NM_001173982.2	c.467_481delTGAAGACCCTGAACC	p.Leu156_Asn160del	disruptive_inframe_deletion	3/3		NP_001167453.1
CHST11	XM_047428914.1	c.245_259delTGAAGACCCTGAACC	p.Leu82_Asn86del	disruptive_inframe_deletion	2/2		XP_047284870.1
CHST11	XM_047428915.1	c.245_259delTGAAGACCCTGAACC	p.Leu82_Asn86del	disruptive_inframe_deletion	2/2		XP_047284871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHST11	ENST00000303694.6	c.482_496delTGAAGACCCTGAACC	p.Leu161_Asn165del	disruptive_inframe_deletion	3/3	1	NM_018413.6	ENSP00000305725.5
CHST11	ENST00000549260.5	c.467_481delTGAAGACCCTGAACC	p.Leu156_Asn160del	disruptive_inframe_deletion	3/3	1		ENSP00000450004.1
CHST11	ENST00000549016.1	c.362_376delTGAAGACCCTGAACC	p.Leu121_Asn125del	disruptive_inframe_deletion	3/3	4		ENSP00000449095.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1 Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Osteochondrodysplasia, brachydactyly, and overlapping malformed digits Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 10, 2019

- -

Brachydactyly;C0343284:Chondrodysplasia;C5574994:Synpolydactyly type 1;na:clino-symphalangism;na:overriding digits Uncertain:1

Uncertain significance, no assertion criteria provided

research

Tolun Lab, Human Genetics Laboratory, Bogazici University

-

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1566067709; hg19: chr12-105150999;