3-43079574-G-T

Variant names:

• chr3-43079574-G-T
• rs75583919
• NM_032806.6:c.*115C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_032806.6(POMGNT2):​c.*115C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00379 in 896,214 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (56 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (20 hom.)
• Consequence: POMGNT2 NM_032806.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.751
• Publications: 0 publications found

Genes affected

POMGNT2 (HGNC:25902): (protein O-linked mannose N-acetylglucosaminyltransferase 2 (beta 1,4-)) This gene encodes a protein with glycosyltransferase activity although its function is not currently known. [provided by RefSeq, Sep 2012]

POMGNT2 Gene-Disease associations (from GenCC):

• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P
• myopathy caused by variation in POMGNT2

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• muscular dystrophy-dystroglycanopathy, type A

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 3-43079574-G-T is Benign according to our data. Variant chr3-43079574-G-T is described in ClinVar as Benign. ClinVar VariationId is 1222363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0145 (2215/152334) while in subpopulation AFR AF = 0.0505 (2101/41564). AF 95% confidence interval is 0.0487. There are 56 homozygotes in GnomAd4. There are 1028 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 56 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032806.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMGNT2	NM_032806.6	MANE Select	c.*115C>A		3_prime_UTR	Exon 2 of 2	NP_116195.2
	POMGNT2	NM_001437285.1		c.*115C>A		3_prime_UTR	Exon 3 of 3	NP_001424214.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMGNT2	ENST00000344697.3	TSL:1 MANE Select	c.*115C>A		3_prime_UTR	Exon 2 of 2	ENSP00000344125.2	Q8NAT1
	POMGNT2	ENST00000441964.1	TSL:4	c.*115C>A		3_prime_UTR	Exon 3 of 3	ENSP00000408992.1	Q8NAT1
	POMGNT2	ENST00000686643.1		c.*115C>A		3_prime_UTR	Exon 4 of 4	ENSP00000509123.1	Q8NAT1

Frequencies

GnomAD3 genomes AF: 0.0145 AC: 2208 AN: 152216 Hom.: 54 Cov.: 33

Gnomad AFR AF: 0.0505

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00484

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.0105

GnomAD4 exome AF: 0.00159 AC: 1185 AN: 743880 Hom.: 20 Cov.: 10 AF XY: 0.00131 AC XY: 496 AN XY: 379052

African (AFR) AF: 0.0482 AC: 860 AN: 17858

American (AMR) AF: 0.00417 AC: 89 AN: 21334

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15474

East Asian (EAS) AF: 0.00 AC: 0 AN: 33218

South Asian (SAS) AF: 0.0000189 AC: 1 AN: 53030

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39774

Middle Eastern (MID) AF: 0.00341 AC: 9 AN: 2640

European-Non Finnish (NFE) AF: 0.000152 AC: 80 AN: 524902

Other (OTH) AF: 0.00410 AC: 146 AN: 35650

GnomAD4 genome AF: 0.0145 AC: 2215 AN: 152334 Hom.: 56 Cov.: 33 AF XY: 0.0138 AC XY: 1028 AN XY: 74496

African (AFR) AF: 0.0505 AC: 2101 AN: 41564

American (AMR) AF: 0.00477 AC: 73 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68034

Other (OTH) AF: 0.0104 AC: 22 AN: 2114

Alfa AF: 0.00372 Hom.: 2

Bravo AF: 0.0167

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.47
PhyloP100		-0.75
Mutation Taster		=100/0	polymorphism

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: rs75583919; hg19: chr3-43121066;