rs1946394691

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017417.2(GALNT8):c.1595A>C(p.Asn532Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000063 in 952,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., cov: 25)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

GALNT8
NM_017417.2 missense, splice_region

Scores

Splicing: ADA: 0.0003027

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.49

Publications

0 publications found

Variant links:

Genes affected

GALNT8 (HGNC:4130): (polypeptide N-acetylgalactosaminyltransferase 8) This gene encodes a member of the UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase (GalNAc-T) family of enzymes. GalNAc-Ts initiate mucin-type O-linked glycosylation in the Golgi apparatus by catalyzing the transfer of GalNAc to serine and threonine residues on target proteins. They are characterized by an N-terminal transmembrane domain, a stem region, a lumenal catalytic domain containing a GT1 motif and Gal/GalNAc transferase motif, and a C-terminal ricin/lectin-like domain. GalNAc-Ts have different, but overlapping, substrate specificities and patterns of expression. [provided by RefSeq, Jul 2008]

GALNT8 links:

ENSG00000255639 (HGNC:):

ENSG00000255639 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.105695784).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALNT8	NM_017417.2 link	c.1595A>C	p.Asn532Thr	missense_variant, splice_region_variant	Exon 10 of 11	ENST00000252318.7	NP_059113.1	Q9NY28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALNT8	ENST00000252318.7 link	c.1595A>C	p.Asn532Thr	missense_variant, splice_region_variant	Exon 10 of 11	1	NM_017417.2	ENSP00000252318.2		Q9NY28
ENSG00000255639	ENST00000648836.1 link	c.1385A>C	p.Asn462Thr	missense_variant, splice_region_variant	Exon 14 of 15			ENSP00000497305.1		A0A3B3ISG8

Frequencies

GnomAD3 genomes

AF:

0.0000176

AC:

AN:

113818

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000109

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000671

GnomAD4 exome

AF:

0.00000477

AC:

AN:

838718

Hom.:

Cov.:

AF XY:

0.00000468

AC XY:

AN XY:

427328

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000529

AC:

AN:

18888

American (AMR)

AF:

0.00

AC:

AN:

23392

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16562

East Asian (EAS)

AF:

0.00

AC:

AN:

30950

South Asian (SAS)

AF:

0.00

AC:

AN:

57234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45934

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2602

European-Non Finnish (NFE)

AF:

0.00000165

AC:

AN:

605794

Other (OTH)

AF:

0.0000535

AC:

AN:

37362

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.021261), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.350

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000176

AC:

AN:

113818

Hom.:

Cov.:

AF XY:

0.0000191

AC XY:

AN XY:

52360

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

29498

American (AMR)

AF:

0.000109

AC:

AN:

9190

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3096

East Asian (EAS)

AF:

0.00

AC:

AN:

3614

South Asian (SAS)

AF:

0.00

AC:

AN:

3400

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3906

Middle Eastern (MID)

AF:

0.00

AC:

AN:

180

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

58662

Other (OTH)

AF:

0.000671

AC:

AN:

1490

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 14, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1595A>C (p.N532T) alteration is located in exon 10 (coding exon 10) of the GALNT8 gene. This alteration results from a A to C substitution at nucleotide position 1595, causing the asparagine (N) at amino acid position 532 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.0065

.;T

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.14

T;T

M_CAP

Benign

0.0060

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

.;L

PhyloP100

1.5

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-2.4

.;N

REVEL

Benign

0.064

Sift

Benign

0.37

.;T

Sift4G

Benign

0.40

.;T

Polyphen

0.10

.;B

Vest4

0.32

MutPred

0.51

.;Loss of sheet (P = 0.0315);

MVP

0.067

MPC

0.11

ClinPred

0.11

GERP RS

2.8

Varity_R

0.12

gMVP

0.24

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00030

dbscSNV1_RF

Benign

0.044

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over