chr2-165748813-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1

The NM_004482.4(GALNT3):c.1870C>T(p.Leu624Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000123 in 1,611,626 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00011 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 1 hom. )

Consequence

GALNT3
NM_004482.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.62

Publications

0 publications found

Variant links:

Genes affected

GALNT3 (HGNC:4125): (polypeptide N-acetylgalactosaminyltransferase 3) This gene encodes UDP-GalNAc transferase 3, a member of the GalNAc-transferases family. This family transfers an N-acetyl galactosamine to the hydroxyl group of a serine or threonine residue in the first step of O-linked oligosaccharide biosynthesis. Individual GalNAc-transferases have distinct activities and initiation of O-glycosylation is regulated by a repertoire of GalNAc-transferases. The protein encoded by this gene is highly homologous to other family members, however the enzymes have different substrate specificities. [provided by RefSeq, Jul 2008]

GALNT3 Gene-Disease associations (from GenCC):

tumoral calcinosis, hyperphosphatemic, familial, 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
tumoral calcinosis, hyperphosphatemic, familial, 1
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, PanelApp Australia

GALNT3 links:

ENSG00000307262 (HGNC:):

ENSG00000307262 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011095703).

BP6

Variant 2-165748813-G-A is Benign according to our data. Variant chr2-165748813-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 715285.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.000124 (181/1459584) while in subpopulation AMR AF = 0.00395 (176/44510). AF 95% confidence interval is 0.00348. There are 1 homozygotes in GnomAdExome4. There are 75 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALNT3	NM_004482.4 link	c.1870C>T	p.Leu624Phe	missense_variant	Exon 11 of 11	ENST00000392701.8	NP_004473.2	Q14435-1
GALNT3	XM_005246449.2 link	c.1870C>T	p.Leu624Phe	missense_variant	Exon 11 of 11		XP_005246506.1	Q14435-1
GALNT3	XM_011510929.2 link	c.1870C>T	p.Leu624Phe	missense_variant	Exon 11 of 11		XP_011509231.1	Q14435-1
GALNT3	XM_017003770.2 link	c.1870C>T	p.Leu624Phe	missense_variant	Exon 11 of 11		XP_016859259.1	Q14435-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GALNT3	ENST00000392701.8 link	c.1870C>T	p.Leu624Phe	missense_variant	Exon 11 of 11	1	NM_004482.4	ENSP00000376465.3	Q14435-1
GALNT3	ENST00000409882.5 link	c.1084C>T	p.Leu362Phe	missense_variant	Exon 8 of 8	1		ENSP00000386955.1	E7EUL0
GALNT3	ENST00000715282.1 link	c.1870C>T	p.Leu624Phe	missense_variant	Exon 11 of 11			ENSP00000520447.1
ENSG00000307262	ENST00000824811.1 link	n.131-984G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00112

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:

0.00

GnomAD2 exomes

AF:

0.000679

AC:

169

AN:

248852

AF XY:

0.000490

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00484

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000493

GnomAD4 exome

AF:

0.000124

AC:

181

AN:

1459584

Hom.:

Cov.:

AF XY:

0.000103

AC XY:

AN XY:

726142

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33402

American (AMR)

AF:

0.00395

AC:

176

AN:

44510

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26068

East Asian (EAS)

AF:

0.00

AC:

AN:

39616

South Asian (SAS)

AF:

0.00

AC:

AN:

86164

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53222

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110612

Other (OTH)

AF:

0.0000829

AC:

AN:

60294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000112

AC:

AN:

152042

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74244

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41420

American (AMR)

AF:

0.00112

AC:

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67974

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000261

Hom.:

Bravo

AF:

0.000287

ExAC

AF:

0.000503

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 08, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.74

DEOGEN2

Benign

0.019

T;.

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.69

T;T

M_CAP

Benign

0.0060

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.4

N;.

PhyloP100

3.6

PrimateAI

Benign

0.43

PROVEAN

Benign

1.3

N;N

REVEL

Benign

0.049

Sift

Benign

0.76

T;T

Sift4G

Benign

0.72

T;T

Polyphen

0.0

B;.

Vest4

0.055

MutPred

0.27

Loss of ubiquitination at K626 (P = 0.073);.;

MVP

0.33

MPC

0.097

ClinPred

0.052

GERP RS

3.8

Varity_R

0.10

gMVP

0.35

Mutation Taster

=96/4

polymorphism

(source)

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

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chr2-165748813-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over