10-43155700-T-A

Variant names:

• chr10-43155700-T-A
• rs138631109
• NM_018590.5:c.551T>A

Variant summary

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

The NM_018590.5(CSGALNACT2):​c.551T>A​(p.Ile184Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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. I184M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CSGALNACT2 NM_018590.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.64
• Publications: 0 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, 0.836

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.551T>A	p.Ile184Asn	missense	Exon 2 of 8	NP_061060.3
	CSGALNACT2	NM_001319654.1		c.551T>A	p.Ile184Asn	missense	Exon 1 of 6	NP_001306583.1	A0A0S2Z5K4
	CSGALNACT2	NM_001319656.1		c.551T>A	p.Ile184Asn	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.551T>A	p.Ile184Asn	missense	Exon 2 of 8	ENSP00000363590.3	Q8N6G5-1
	CSGALNACT2	ENST00000943044.1		c.551T>A	p.Ile184Asn	missense	Exon 2 of 9	ENSP00000613103.1
	CSGALNACT2	ENST00000908296.1		c.551T>A	p.Ile184Asn	missense	Exon 2 of 8	ENSP00000578355.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251410 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.035	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		7.6
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.93	P
Vest4		0.89
MutPred		0.67		Loss of stability (P = 0.3138)
MVP		0.81
MPC		0.91
ClinPred		0.99	D
GERP RS		4.7
Varity_R		0.81
gMVP		0.89
Mutation Taster		=46/54	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: rs138631109; hg19: chr10-43651148;