11-45650425-C-A

Variant names:

• chr11-45650425-C-A
• rs1446720680
• NM_003654.6:c.499G>T

Variant summary

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

The NM_003654.6(CHST1):​c.499G>T​(p.Asp167Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,456,392 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. D167H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CHST1 NM_003654.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.80

Genes affected

CHST1 (HGNC:1969): (carbohydrate sulfotransferase 1) This locus encodes a member of the keratin sulfotransferase family of proteins. The encoded enzyme catalyzes the sulfation of the proteoglycan keratin. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 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
CHST1	NM_003654.6	c.499G>T	p.Asp167Tyr	missense_variant	Exon 4 of 4	ENST00000308064.7	NP_003645.1
CHST1	XM_006718356.5	c.499G>T	p.Asp167Tyr	missense_variant	Exon 4 of 5		XP_006718419.1
CHST1	XM_017018459.3	c.499G>T	p.Asp167Tyr	missense_variant	Exon 4 of 5		XP_016873948.1
CHST1	XM_047427781.1	c.499G>T	p.Asp167Tyr	missense_variant	Exon 4 of 4		XP_047283737.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHST1	ENST00000308064.7	c.499G>T	p.Asp167Tyr	missense_variant	Exon 4 of 4	1	NM_003654.6	ENSP00000309270.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000409 AC: 1 AN: 244248 Hom.: 0 AF XY: 0.00000752 AC XY: 1 AN XY: 132994

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: 0.00

Gnomad NFE exome AF: 0.00000896

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456392 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 724832

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: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.72	D
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.48	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Pathogenic	0.86	D
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-2.9	D
REVEL	Pathogenic	0.71
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.033	D
Polyphen		0.92	P
Vest4		0.32
MutPred		0.51		Loss of disorder (P = 0.0089);
MVP		0.81
MPC		2.1
ClinPred		0.93	D
GERP RS		3.5
Varity_R		0.21
gMVP		0.85

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: rs1446720680; hg19: chr11-45671975;