15-40471501-G-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_130468.4(CHST14):c.288G>T(p.Arg96Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000552 in 1,448,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. R96R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

CHST14
NM_130468.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.67

Publications

1 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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.054608136).

BP6

Variant 15-40471501-G-T is Benign according to our data. Variant chr15-40471501-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3492710.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 link	c.288G>T	p.Arg96Ser	missense_variant	Exon 1 of 1	ENST00000306243.7	NP_569735.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
CHST14	ENST00000306243.7 link	c.288G>T	p.Arg96Ser	missense_variant	Exon 1 of 1	6	NM_130468.4	ENSP00000307297.6
CHST14	ENST00000559991.1 link	c.288G>T	p.Arg96Ser	missense_variant	Exon 1 of 2	5		ENSP00000453882.1
ENSG00000302612	ENST00000788112.1 link	n.151+154C>A		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000552

AC:

AN:

1448362

Hom.:

Cov.:

AF XY:

0.00000417

AC XY:

AN XY:

720008

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33318

American (AMR)

AF:

0.00

AC:

AN:

44364

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25934

East Asian (EAS)

AF:

0.00

AC:

AN:

39544

South Asian (SAS)

AF:

0.00

AC:

AN:

85876

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45192

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.00000631

AC:

AN:

1108478

Other (OTH)

AF:

0.0000167

AC:

AN:

59912

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Cardiovascular phenotype

Benign:1

Mar 27, 2025

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.26

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.0096

T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.25

T;T

M_CAP

Benign

0.030

MetaRNN

Benign

0.055

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.0

N;.

PhyloP100

-1.7

PrimateAI

Benign

0.45

PROVEAN

Benign

0.98

N;N

REVEL

Benign

0.10

Sift

Benign

0.84

T;T

Sift4G

Benign

0.70

T;T

Vest4

0.021

ClinPred

0.031

GERP RS

-7.8

PromoterAI

-0.024

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.15

gMVP

0.43

Mutation Taster

=92/8

polymorphism

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over