10-43183348-C-T

Position:

• chr10-43183348-C-T

Variant summary

Our verdict is Benign. Variant got -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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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]

CSGALNACT2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSGALNACT2	NM_018590.5	c.1435C>T	p.Pro479Ser	missense_variant	8/8	ENST00000374466.4	NP_061060.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSGALNACT2	ENST00000374466.4	c.1435C>T	p.Pro479Ser	missense_variant	8/8	1	NM_018590.5	ENSP00000363590.3

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

GnomAD3 exomes AF: 0.232 AC: 58350 AN: 251466 Hom.: 7472 AF XY: 0.235 AC XY: 31975 AN XY: 135910

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 SAS exome AF: 0.170

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

Gnomad4 AFR exome AF: 0.0547

Gnomad4 AMR exome AF: 0.173

Gnomad4 ASJ exome AF: 0.226

Gnomad4 EAS exome AF: 0.215

Gnomad4 SAS exome AF: 0.173

Gnomad4 FIN exome AF: 0.308

Gnomad4 NFE exome AF: 0.275

Gnomad4 OTH exome AF: 0.242

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

Gnomad4 AFR AF: 0.0665

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.213

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 v4.3

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
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

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