chr2-165747846-T-TA

Variant names:

• chr2-165747846-T-TA
• rs144647329
• NM_004482.4:c.*934dupT

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The NM_004482.4(GALNT3):​c.*934dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00334 in 170,736 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (0 hom.)
• Consequence: GALNT3 NM_004482.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.153
• Publications: 0 publications found

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

ENSG00000307262 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00348 (529/152064) while in subpopulation AMR AF = 0.00964 (147/15254). AF 95% confidence interval is 0.00837. There are 5 homozygotes in GnomAd4. There are 250 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALNT3	NM_004482.4	c.*934dupT		3_prime_UTR_variant	Exon 11 of 11	ENST00000392701.8	NP_004473.2
GALNT3	XM_005246449.2	c.*934dupT		3_prime_UTR_variant	Exon 11 of 11		XP_005246506.1
GALNT3	XM_011510929.2	c.*934dupT		3_prime_UTR_variant	Exon 11 of 11		XP_011509231.1
GALNT3	XM_017003770.2	c.*934dupT		3_prime_UTR_variant	Exon 11 of 11		XP_016859259.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALNT3	ENST00000392701.8	c.*934dupT		3_prime_UTR_variant	Exon 11 of 11	1	NM_004482.4	ENSP00000376465.3
GALNT3	ENST00000409882.5	c.*934dupT		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000386955.1
ENSG00000307262	ENST00000824811.1	n.130+930dupA		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.00348 AC: 529 AN: 151946 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00681

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00965

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000946

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00107

Gnomad OTH AF: 0.00672

GnomAD4 exome AF: 0.00220 AC: 41 AN: 18672 Hom.: 0 Cov.: 0 AF XY: 0.00143 AC XY: 12 AN XY: 8420

African (AFR) AF: 0.0109 AC: 7 AN: 640

American (AMR) AF: 0.00980 AC: 4 AN: 408

Ashkenazi Jewish (ASJ) AF: 0.00192 AC: 2 AN: 1044

East Asian (EAS) AF: 0.00 AC: 0 AN: 4238

South Asian (SAS) AF: 0.00 AC: 0 AN: 156

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 102

European-Non Finnish (NFE) AF: 0.00191 AC: 20 AN: 10496

Other (OTH) AF: 0.00506 AC: 8 AN: 1580

GnomAD4 genome AF: 0.00348 AC: 529 AN: 152064 Hom.: 5 Cov.: 32 AF XY: 0.00336 AC XY: 250 AN XY: 74338

African (AFR) AF: 0.00681 AC: 283 AN: 41528

American (AMR) AF: 0.00964 AC: 147 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.0000946 AC: 1 AN: 10572

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00106 AC: 72 AN: 67936

Other (OTH) AF: 0.00665 AC: 14 AN: 2106

Alfa AF: 0.000650 Hom.: 0

Bravo AF: 0.00480

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Familial hyperphosphatemic tumoral calcinosis/hyperphosphatemic hyperostosis syndrome Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.15

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

Other links and lift over

dbSNP: rs144647329; hg19: chr2-166604356;