rs1043447552

Positions:

• chr15-40471343-A-C
• chr15-40471343-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_130468.4(CHST14):​c.130A>C​(p.Met44Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,396,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: CHST14 NM_130468.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.43

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11039743).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHST14	NM_130468.4	c.130A>C	p.Met44Leu	missense_variant	1/1	ENST00000306243.7	NP_569735.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHST14	ENST00000306243.7	c.130A>C	p.Met44Leu	missense_variant	1/1		NM_130468.4	ENSP00000307297	P1
CHST14	ENST00000559991.1	c.130A>C	p.Met44Leu	missense_variant	1/2	5		ENSP00000453882

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000663 AC: 1 AN: 150884 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 82050

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000127

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.16e-7 AC: 1 AN: 1396416 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 690234

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000265

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	21
DANN	Benign	0.93
DEOGEN2	Benign	0.038	T;.
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.70	T;T
M_CAP	Uncertain	0.094	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.55	N;.
MutationTaster	Benign	0.94	D;D
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.62	N;N
REVEL	Benign	0.076
Sift	Benign	0.11	T;T
Sift4G	Benign	0.27	T;T
Polyphen		0.035	B;.
Vest4		0.18
MutPred		0.34		Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);
MVP		0.47
MPC		0.85
ClinPred		0.26	T
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.21
gMVP		0.39

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

LitVar

Other links and lift over

dbSNP: rs1043447552; hg19: chr15-40763542;