8-19405492-G-A

Variant names:

• chr8-19405492-G-A
• rs3802330
• NM_001354483.2:c.*288C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001354483.2(CSGALNACT1):​c.*288C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 575,906 control chromosomes in the GnomAD database, including 129,439 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (29460 hom., cov: 32)
  • Exomes 𝑓: 0.68 (99979 hom.)
• Consequence: CSGALNACT1 NM_001354483.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.26

Genes affected

CSGALNACT1 (HGNC:24290): (chondroitin sulfate N-acetylgalactosaminyltransferase 1) This gene encodes an enzyme that transfers N-acetylglucosamine (GalNAc) to the core tetrasaccharide linker and to elongating chondroitin sulfate chains in proteoglycans. Knockout of the orthologous mouse gene indicates that the protein is necessary for normal cartilage development and aggrecan metabolism. Mutations in this gene are associated with multiple sclerosis progression, and with mild skeletal dysplasia and joint laxity. [provided by RefSeq, Aug 2017]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 8-19405492-G-A is Benign according to our data. Variant chr8-19405492-G-A is described in ClinVar as [Benign]. Clinvar id is 1274315.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSGALNACT1	NM_001354483.2	c.*288C>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000692225.2	NP_001341412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSGALNACT1	ENST00000692225	c.*288C>T		3_prime_UTR_variant	Exon 9 of 9		NM_001354483.2	ENSP00000509853.1

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91721 AN: 151874 Hom.: 29442 Cov.: 32

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.974

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.665

Gnomad OTH AF: 0.604

GnomAD2 exomes AF: 0.699 AC: 91595 AN: 131020 AF XY: 0.693

Gnomad AFR exome AF: 0.379

Gnomad AMR exome AF: 0.806

Gnomad ASJ exome AF: 0.623

Gnomad EAS exome AF: 0.974

Gnomad FIN exome AF: 0.681

Gnomad NFE exome AF: 0.661

Gnomad OTH exome AF: 0.655

GnomAD4 exome AF: 0.680 AC: 288114 AN: 423914 Hom.: 99979 Cov.: 3 AF XY: 0.678 AC XY: 158114 AN XY: 233278

Gnomad4 AFR exome AF: 0.391 AC: 5104 AN: 13044

Gnomad4 AMR exome AF: 0.800 AC: 24679 AN: 30864

Gnomad4 ASJ exome AF: 0.630 AC: 10023 AN: 15916

Gnomad4 EAS exome AF: 0.973 AC: 19234 AN: 19776

Gnomad4 SAS exome AF: 0.667 AC: 40507 AN: 60746

Gnomad4 FIN exome AF: 0.681 AC: 13879 AN: 20388

Gnomad4 NFE exome AF: 0.664 AC: 158579 AN: 238646

Gnomad4 Remaining exome AF: 0.663 AC: 15070 AN: 22722

GnomAD4 genome AF: 0.604 AC: 91773 AN: 151992 Hom.: 29460 Cov.: 32 AF XY: 0.611 AC XY: 45384 AN XY: 74296

Gnomad4 AFR AF: 0.382 AC: 0.381622 AN: 0.381622

Gnomad4 AMR AF: 0.720 AC: 0.719982 AN: 0.719982

Gnomad4 ASJ AF: 0.628 AC: 0.627598 AN: 0.627598

Gnomad4 EAS AF: 0.974 AC: 0.973766 AN: 0.973766

Gnomad4 SAS AF: 0.666 AC: 0.665768 AN: 0.665768

Gnomad4 FIN AF: 0.690 AC: 0.690291 AN: 0.690291

Gnomad4 NFE AF: 0.665 AC: 0.665098 AN: 0.665098

Gnomad4 OTH AF: 0.606 AC: 0.605587 AN: 0.605587

Alfa AF: 0.653 Hom.: 99135

Bravo AF: 0.598

Asia WGS AF: 0.772 AC: 2682 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.4
DANN	Benign	0.62
Mutation Taster		=100/0	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

Publications

LitVar

Other links and lift over

dbSNP: rs3802330; hg19: chr8-19263003;