chr10-43155706-C-T

Variant names:

• chr10-43155706-C-T
• rs760121385
• NM_018590.5:c.557C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_018590.5(CSGALNACT2):​c.557C>T​(p.Ala186Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000088 in 1,613,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000089 (0 hom.)
• Consequence: CSGALNACT2 NM_018590.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.54
• Publications: 1 publications found

Genes affected

CSGALNACT2 (HGNC:24292): (chondroitin sulfate N-acetylgalactosaminyltransferase 2) This gene encodes a member of the chondroitin N-acetylgalactosaminyltransferase family. The encoded protein is involved in elongation during chondroitin sulfate synthesis. Alternative splicing of this gene results in multiple transcript variants. Two related pseudogenes have been identified on chromosome X. [provided by RefSeq, Feb 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.763

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018590.5. 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
	CSGALNACT2	NM_018590.5	MANE Select	c.557C>T	p.Ala186Val	missense	Exon 2 of 8	NP_061060.3
	CSGALNACT2	NM_001319654.1		c.557C>T	p.Ala186Val	missense	Exon 1 of 6	NP_001306583.1	A0A0S2Z5K4
	CSGALNACT2	NM_001319656.1		c.557C>T	p.Ala186Val	missense	Exon 1 of 5	NP_001306585.1	Q8N6G5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSGALNACT2	ENST00000374466.4	TSL:1 MANE Select	c.557C>T	p.Ala186Val	missense	Exon 2 of 8	ENSP00000363590.3	Q8N6G5-1
	CSGALNACT2	ENST00000943044.1		c.557C>T	p.Ala186Val	missense	Exon 2 of 9	ENSP00000613103.1
	CSGALNACT2	ENST00000908296.1		c.557C>T	p.Ala186Val	missense	Exon 2 of 8	ENSP00000578355.1

Frequencies

GnomAD3 genomes AF: 0.0000789 AC: 12 AN: 152122 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000517 AC: 13 AN: 251384 AF XY: 0.0000442

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 FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.0000967

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000889 AC: 130 AN: 1461834 Hom.: 0 Cov.: 31 AF XY: 0.0000866 AC XY: 63 AN XY: 727218

African (AFR) AF: 0.000119 AC: 4 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000106 AC: 118 AN: 1111970

Other (OTH) AF: 0.0000662 AC: 4 AN: 60394

GnomAD4 genome AF: 0.0000789 AC: 12 AN: 152122 Hom.: 0 Cov.: 33 AF XY: 0.0000808 AC XY: 6 AN XY: 74296

African (AFR) AF: 0.0000724 AC: 3 AN: 41424

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000113 Hom.: 0

Bravo AF: 0.0000567

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.016	T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.027	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.5	L
PhyloP100		7.5
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.24
Sift	Benign	0.54	T
Sift4G	Benign	0.52	T
Polyphen		1.0	D
Vest4		0.82
MVP		0.76
MPC		0.72
ClinPred		0.47	T
GERP RS		5.8
Varity_R		0.21
gMVP		0.57
Mutation Taster		=24/76	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: rs760121385; hg19: chr10-43651154; COSMIC: COSV65675073;