Genetic Variant CHST14:p.Pro17Thr (chr15-40471262-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_130468.4(CHST14):c.49C>A(p.Pro17Thr) variant causes a missense 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P17S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CHST14
NM_130468.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.411

Publications

0 publications found

Variant links:

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

CHST14 links:

ENSG00000302612 (HGNC:):

ENSG00000302612 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06501922).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130468.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST14	NM_130468.4	MANE Select	c.49C>A	p.Pro17Thr	missense	Exon 1 of 1	NP_569735.1	Q8NCH0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHST14	ENST00000306243.7	TSL:6 MANE Select	c.49C>A	p.Pro17Thr	missense	Exon 1 of 1	ENSP00000307297.6	Q8NCH0
CHST14	ENST00000559991.1	TSL:5	c.49C>A	p.Pro17Thr	missense	Exon 1 of 2	ENSP00000453882.1	H0YN65
ENSG00000302612	ENST00000788112.1		n.151+393G>T		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1340308

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

661090

African (AFR)

AF:

0.00

AC:

AN:

26740

American (AMR)

AF:

0.00

AC:

AN:

29000

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23042

East Asian (EAS)

AF:

0.00

AC:

AN:

31486

South Asian (SAS)

AF:

0.00

AC:

AN:

74504

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33818

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4060

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1061964

Other (OTH)

AF:

0.00

AC:

AN:

55694

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000235

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.013

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.47

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.065

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

PhyloP100

-0.41

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

0.16

REVEL

Benign

0.15

Sift

Benign

0.75

Sift4G

Benign

0.62

Polyphen

0.0

Vest4

0.064

MutPred

0.18

Gain of helix (P = 0.0034)

MVP

0.15

MPC

1.0

ClinPred

0.12

GERP RS

0.45

PromoterAI

-0.058

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.057

gMVP

0.38

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over