2-165748461-C-CTA

Variant names:

• chr2-165748461-C-CTA
• rs140333197
• NM_004482.4:c.*318_*319dupTA

Variant summary

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

The NM_004482.4(GALNT3):​c.*318_*319dupTA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000452 in 343,188 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00034 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00054 (0 hom.)
• Consequence: GALNT3 NM_004482.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.300
• 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALNT3	NM_004482.4	c.*318_*319dupTA		3_prime_UTR_variant	Exon 11 of 11	ENST00000392701.8	NP_004473.2
GALNT3	XM_005246449.2	c.*318_*319dupTA		3_prime_UTR_variant	Exon 11 of 11		XP_005246506.1
GALNT3	XM_011510929.2	c.*318_*319dupTA		3_prime_UTR_variant	Exon 11 of 11		XP_011509231.1
GALNT3	XM_017003770.2	c.*318_*319dupTA		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.*318_*319dupTA		3_prime_UTR_variant	Exon 11 of 11	1	NM_004482.4	ENSP00000376465.3
GALNT3	ENST00000409882.5	c.*318_*319dupTA		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000386955.1
GALNT3	ENST00000715282.1	c.*318_*319dupTA		3_prime_UTR_variant	Exon 11 of 11			ENSP00000520447.1
ENSG00000307262	ENST00000824811.1	n.131-1324_131-1323dupAT		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.000351 AC: 53 AN: 151164 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000792

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00323

Gnomad NFE AF: 0.000458

Gnomad OTH AF: 0.000484

GnomAD4 exome AF: 0.000537 AC: 103 AN: 191914 Hom.: 0 Cov.: 0 AF XY: 0.000607 AC XY: 59 AN XY: 97272

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

African (AFR) AF: 0.000327 AC: 2 AN: 6124

American (AMR) AF: 0.000456 AC: 3 AN: 6578

Ashkenazi Jewish (ASJ) AF: 0.000266 AC: 2 AN: 7514

East Asian (EAS) AF: 0.00 AC: 0 AN: 15074

South Asian (SAS) AF: 0.000450 AC: 9 AN: 19990

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6576

Middle Eastern (MID) AF: 0.00346 AC: 3 AN: 868

European-Non Finnish (NFE) AF: 0.000650 AC: 76 AN: 117006

Other (OTH) AF: 0.000657 AC: 8 AN: 12184

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000344 AC: 52 AN: 151274 Hom.: 0 Cov.: 32 AF XY: 0.000298 AC XY: 22 AN XY: 73882

African (AFR) AF: 0.0000242 AC: 1 AN: 41332

American (AMR) AF: 0.000791 AC: 12 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.000388 AC: 2 AN: 5160

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4792

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.000458 AC: 31 AN: 67656

Other (OTH) AF: 0.000479 AC: 1 AN: 2088

Alfa AF: 0.000108 Hom.: 0

Bravo AF: 0.000329

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		0.30
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs140333197; hg19: chr2-166604971;