chr8-19405817-C-G

Position:

chr8-19405817-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001354483.2(CSGALNACT1):c.1562G>C(p.Arg521Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0053 in 1,614,096 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0037 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0055 ( 32 hom. )

Consequence

CSGALNACT1
NM_001354483.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 4.71

Variant links:

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]

CSGALNACT1 links:

CSGALNACT1 (HGNC:):

CSGALNACT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0078080297).

BP6

Variant 8-19405817-C-G is Benign according to our data. Variant chr8-19405817-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1599898.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00369 (561/152214) while in subpopulation NFE AF= 0.00618 (420/68006). AF 95% confidence interval is 0.00569. There are 4 homozygotes in gnomad4. There are 249 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSGALNACT1	NM_001354483.2 linkuse as main transcript	c.1562G>C	p.Arg521Pro	missense_variant	9/9	ENST00000692225.2	NP_001341412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSGALNACT1	ENST00000692225.2 linkuse as main transcript	c.1562G>C	p.Arg521Pro	missense_variant	9/9		NM_001354483.2	ENSP00000509853.1		Q8TDX6-1

Frequencies

GnomAD3 genomes

AF:

0.00369

AC:

561

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00268

Gnomad ASJ

AF:

0.00865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00618

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00388

AC:

976

AN:

251434

Hom.:

AF XY:

0.00395

AC XY:

537

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00231

Gnomad ASJ exome

AF:

0.00615

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00101

Gnomad FIN exome

AF:

0.00194

Gnomad NFE exome

AF:

0.00646

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00547

AC:

8000

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00533

AC XY:

3873

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.000956

Gnomad4 AMR exome

AF:

0.00233

Gnomad4 ASJ exome

AF:

0.00735

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000985

Gnomad4 FIN exome

AF:

0.00210

Gnomad4 NFE exome

AF:

0.00651

Gnomad4 OTH exome

AF:

0.00391

GnomAD4 genome

AF:

0.00369

AC:

561

AN:

152214

Hom.:

Cov.:

AF XY:

0.00335

AC XY:

249

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.00104

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.00865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00189

Gnomad4 NFE

AF:

0.00618

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00516

Hom.:

Bravo

AF:

0.00359

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00570

AC:

ExAC

AF:

0.00413

AC:

501

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00431

EpiControl

AF:

0.00504

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2024	CSGALNACT1: BP4, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

CSGALNACT1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 03, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.65

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Uncertain

-0.070

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

T;T;T

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

.;.;D

M_CAP

Benign

0.028

MetaRNN

Benign

0.0078

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;M;M

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.5

N;N;N

REVEL

Benign

0.15

Sift

Uncertain

0.016

D;D;D

Sift4G

Uncertain

0.021

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.55

MVP

0.44

MPC

0.15

ClinPred

0.025

GERP RS

5.9

Varity_R

0.64

gMVP

0.72

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over