rs267606727

Variant names:

• chr15-40471616-C-G
• rs267606727
• NM_130468.4:c.403C>G

Your query was ambiguous. Multiple possible variants found:

• chr15-40471616-C-G
• chr15-40471616-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_130468.4(CHST14):​c.403C>G​(p.Arg135Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as no classification for the single variant (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHST14 NM_130468.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.78
• Publications: 6 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

ENSG00000302612 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST14	NM_130468.4	MANE Select	c.403C>G	p.Arg135Gly	missense	Exon 1 of 1	NP_569735.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST14	ENST00000306243.7	TSL:6 MANE Select	c.403C>G	p.Arg135Gly	missense	Exon 1 of 1	ENSP00000307297.6
	CHST14	ENST00000559991.1	TSL:5	c.403C>G	p.Arg135Gly	missense	Exon 1 of 2	ENSP00000453882.1
	ENSG00000302612	ENST00000788112.1		n.151+39G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.058	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.8
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.019	D
Polyphen		0.86	P
Vest4		0.35
MutPred		0.66		Loss of MoRF binding (P = 0.0142)
MVP		0.94
MPC		1.7
ClinPred		0.95	D
GERP RS		4.6
Varity_R		0.41
gMVP		0.67
Mutation Taster		=16/84	disease causing

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: rs267606727; hg19: chr15-40763815;