11-45650296-C-A

Variant names:

• chr11-45650296-C-A
• rs746564532
• NM_003654.6:c.628G>T

Variant summary

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

The NM_003654.6(CHST1):​c.628G>T​(p.Val210Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. V210M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CHST1 NM_003654.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.27
• Publications: 2 publications found

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

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_003654.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST1	NM_003654.6	MANE Select	c.628G>T	p.Val210Leu	missense	Exon 4 of 4	NP_003645.1	O43916

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST1	ENST00000308064.7	TSL:1 MANE Select	c.628G>T	p.Val210Leu	missense	Exon 4 of 4	ENSP00000309270.2	O43916
	CHST1	ENST00000891796.1		c.628G>T	p.Val210Leu	missense	Exon 4 of 4	ENSP00000561855.1
	CHST1	ENST00000891797.1		c.628G>T	p.Val210Leu	missense	Exon 4 of 4	ENSP00000561856.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.42	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.073	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.52	T
PhyloP100		3.3
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.48	N
REVEL	Uncertain	0.37
Sift	Benign	0.10	T
Sift4G	Benign	0.17	T
Polyphen		0.89	P
Vest4		0.62
MutPred		0.50		Gain of catalytic residue at V210 (P = 0.0046)
MVP		0.85
MPC		1.7
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.10
gMVP		0.96
Mutation Taster		=83/17	polymorphism

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: rs746564532; hg19: chr11-45671846;