rs2435381

Variant names:

• chr10-43183348-C-T
• rs2435381
• NM_018590.5:c.1435C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018590.5(CSGALNACT2):​c.1435C>T​(p.Pro479Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 1,613,590 control chromosomes in the GnomAD database, including 54,615 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 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: 𝑓 0.21 (3953 hom., cov: 32)
  • Exomes 𝑓: 0.26 (50662 hom.)
• Consequence: CSGALNACT2 NM_018590.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.96
• Publications: 20 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014256835).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

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.1435C>T	p.Pro479Ser	missense	Exon 8 of 8	NP_061060.3
	CSGALNACT2	NM_001319654.1		c.*89C>T		3_prime_UTR	Exon 6 of 6	NP_001306583.1	A0A0S2Z5K4
	CSGALNACT2	NM_001319656.1		c.*132C>T		3_prime_UTR	Exon 5 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.1435C>T	p.Pro479Ser	missense	Exon 8 of 8	ENSP00000363590.3	Q8N6G5-1
	CSGALNACT2	ENST00000943044.1		c.1453C>T	p.Pro485Ser	missense	Exon 9 of 9	ENSP00000613103.1
	CSGALNACT2	ENST00000908296.1		c.1435C>T	p.Pro479Ser	missense	Exon 8 of 8	ENSP00000578355.1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31637 AN: 151930 Hom.: 3943 Cov.: 32

Gnomad AFR AF: 0.0666

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.207

GnomAD2 exomes AF: 0.232 AC: 58350 AN: 251466 AF XY: 0.235

Gnomad AFR exome AF: 0.0632

Gnomad AMR exome AF: 0.169

Gnomad ASJ exome AF: 0.229

Gnomad EAS exome AF: 0.232

Gnomad FIN exome AF: 0.319

Gnomad NFE exome AF: 0.275

Gnomad OTH exome AF: 0.237

GnomAD4 exome AF: 0.258 AC: 377267 AN: 1461542 Hom.: 50662 Cov.: 34 AF XY: 0.256 AC XY: 186359 AN XY: 727090

African (AFR) AF: 0.0547 AC: 1832 AN: 33472

American (AMR) AF: 0.173 AC: 7750 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 5912 AN: 26134

East Asian (EAS) AF: 0.215 AC: 8528 AN: 39698

South Asian (SAS) AF: 0.173 AC: 14954 AN: 86248

European-Finnish (FIN) AF: 0.308 AC: 16457 AN: 53418

Middle Eastern (MID) AF: 0.208 AC: 1202 AN: 5766

European-Non Finnish (NFE) AF: 0.275 AC: 305994 AN: 1111710

Other (OTH) AF: 0.242 AC: 14638 AN: 60374

GnomAD4 genome AF: 0.208 AC: 31662 AN: 152048 Hom.: 3953 Cov.: 32 AF XY: 0.212 AC XY: 15740 AN XY: 74324

African (AFR) AF: 0.0665 AC: 2761 AN: 41500

American (AMR) AF: 0.211 AC: 3225 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 798 AN: 3470

East Asian (EAS) AF: 0.229 AC: 1181 AN: 5162

South Asian (SAS) AF: 0.167 AC: 806 AN: 4814

European-Finnish (FIN) AF: 0.324 AC: 3415 AN: 10536

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18655 AN: 67974

Other (OTH) AF: 0.213 AC: 450 AN: 2108

Alfa AF: 0.230 Hom.: 2179

Bravo AF: 0.193

TwinsUK AF: 0.270 AC: 1001

ALSPAC AF: 0.272 AC: 1047

ESP6500AA AF: 0.0695 AC: 306

ESP6500EA AF: 0.267 AC: 2293

ExAC AF: 0.232 AC: 28127

Asia WGS AF: 0.189 AC: 656 AN: 3478

EpiCase AF: 0.275

EpiControl AF: 0.273

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.098	T
Eigen	Benign	0.091
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.91	L
PhyloP100		3.0
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.12
Sift	Benign	0.19	T
Sift4G	Benign	0.20	T
Polyphen		0.13	B
Vest4		0.034
MPC		0.23
ClinPred		0.026	T
GERP RS		5.9
Varity_R		0.12
gMVP		0.61
Mutation Taster		=53/47	polymorphism (auto)

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: rs2435381; hg19: chr10-43678796; COSMIC: COSV65676651;