chr2-165748461-C-CTA

Position:

• chr2-165748461-C-CTA

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BS1_Supporting

The NM_004482.4(GALNT3):​c.*319_*320insTA 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. Variant has been reported in ClinVar as Uncertain significance (★).

• 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000537 (103/191914) while in subpopulation MID AF= 0.00346 (3/868). AF 95% confidence interval is 0.000942. There are 0 homozygotes in gnomad4_exome. There are 59 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALNT3	NM_004482.4	c.*319_*320insTA		3_prime_UTR_variant	11/11	ENST00000392701.8
GALNT3	XM_005246449.2	c.*319_*320insTA		3_prime_UTR_variant	11/11
GALNT3	XM_011510929.2	c.*319_*320insTA		3_prime_UTR_variant	11/11
GALNT3	XM_017003770.2	c.*319_*320insTA		3_prime_UTR_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALNT3	ENST00000392701.8	c.*319_*320insTA		3_prime_UTR_variant	11/11	1	NM_004482.4	P1
GALNT3	ENST00000409882.5	c.*319_*320insTA		3_prime_UTR_variant	8/8	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

Gnomad4 AFR exome AF: 0.000327

Gnomad4 AMR exome AF: 0.000456

Gnomad4 ASJ exome AF: 0.000266

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000450

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000650

Gnomad4 OTH exome AF: 0.000657

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

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.000791

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000458

Gnomad4 OTH AF: 0.000479

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

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs140333197; hg19: chr2-166604971;