dbSNP rs752758290: 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: Genomics England PanelApp, G2P, PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
Ehlers-Danlos syndrome, musculocontractural type
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CHST14 links:

ENSG00000302612 (HGNC:):

ENSG00000302612 links:

Genome browser will be placed here

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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST14	NM_130468.4 link	c.49C>A	p.Pro17Thr	missense_variant	Exon 1 of 1	ENST00000306243.7	NP_569735.1	Q8NCH0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CHST14	ENST00000306243.7 link	c.49C>A	p.Pro17Thr	missense_variant	Exon 1 of 1	6	NM_130468.4	ENSP00000307297.6	Q8NCH0
CHST14	ENST00000559991.1 link	c.49C>A	p.Pro17Thr	missense_variant	Exon 1 of 2	5		ENSP00000453882.1	H0YN65
ENSG00000302612	ENST00000788112.1 link	n.151+393G>T		intron_variant	Intron 1 of 4

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 v4.3

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

T;.

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.47

T;T

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.065

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

N;.

PhyloP100

-0.41

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

0.16

N;N

REVEL

Benign

0.15

Sift

Benign

0.75

T;T

Sift4G

Benign

0.62

T;T

Polyphen

0.0

B;.

Vest4

0.064

MutPred

0.18

Gain of helix (P = 0.0034);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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over