rs267606728

Variant names:

• chr15-40471623-T-A
• rs267606728
• NM_130468.4:c.410T>A

Your query was ambiguous. Multiple possible variants found:

• chr15-40471623-T-A
• chr15-40471623-T-C

Variant summary

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

The NM_130468.4(CHST14):​c.410T>A​(p.Leu137Gln) 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). Synonymous variant affecting the same amino acid position (i.e. L137L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHST14 NM_130468.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.24
• Publications: 7 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST14	NM_130468.4	c.410T>A	p.Leu137Gln	missense_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.410T>A	p.Leu137Gln	missense_variant	Exon 1 of 1	6	NM_130468.4	ENSP00000307297.6
CHST14	ENST00000559991.1	c.410T>A	p.Leu137Gln	missense_variant	Exon 1 of 2	5		ENSP00000453882.1
ENSG00000302612	ENST00000788112.1	n.151+32A>T		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.33
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T;.
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.87	D;T
M_CAP	Uncertain	0.088	D
MetaRNN	Uncertain	0.54	D;D
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	1.9	L;.
PhyloP100		3.2
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Uncertain	0.64
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0040	D;D
Polyphen		1.0	D;.
Vest4		0.38
MutPred		0.78		Loss of stability (P = 0.0202);Loss of stability (P = 0.0202);
MVP		1.0
MPC		2.0
ClinPred		0.97	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.67
gMVP		0.56
Mutation Taster		=23/77	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: rs267606728; hg19: chr15-40763822;