15-40472062-C-T

Variant names:

• chr15-40472062-C-T
• rs1438289059
• NM_130468.4:c.849C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_130468.4(CHST14):​c.849C>T​(p.Tyr283Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHST14 NM_130468.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.41
• Publications: 0 publications found

Genes affected

CHST14 (HGNC:24464): (carbohydrate sulfotransferase 14) This gene encodes a member of the HNK-1 family of sulfotransferases. The encoded protein transfers sulfate to the C-4 hydroxyl of N-acetylgalactosamine residues in dermatan sulfate. Mutations in this gene have been associated with adducted thumb-clubfoot syndrome.[provided by RefSeq, Mar 2010]

CHST14 Gene-Disease associations (from GenCC):

• Ehlers-Danlos syndrome, musculocontractural type 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P, PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Ehlers-Danlos syndrome, musculocontractural type

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 15-40472062-C-T is Benign according to our data. Variant chr15-40472062-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 536425.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST14	NM_130468.4	c.849C>T	p.Tyr283Tyr	synonymous_variant	Exon 1 of 1	ENST00000306243.7	NP_569735.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHST14	ENST00000306243.7	c.849C>T	p.Tyr283Tyr	synonymous_variant	Exon 1 of 1	6	NM_130468.4	ENSP00000307297.6
CHST14	ENST00000559991.1	c.774C>T	p.Tyr258Tyr	synonymous_variant	Exon 2 of 2	5		ENSP00000453882.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Ehlers-Danlos syndrome, musculocontractural type Benign:1

Dec 17, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	11
DANN	Benign	0.91
PhyloP100		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs1438289059; hg19: chr15-40764261;