rs141319921

Variant names:

• chr3-43080466-G-A
• rs141319921
• NM_032806.6:c.966C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-43080466-G-A
• chr3-43080466-G-C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_032806.6(POMGNT2):​c.966C>T​(p.Ser322Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S322S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: POMGNT2 NM_032806.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47
• 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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP7: Synonymous conserved (PhyloP=1.47 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POMGNT2	NM_032806.6	c.966C>T	p.Ser322Ser	synonymous_variant	Exon 2 of 2	ENST00000344697.3	NP_116195.2
POMGNT2	NM_001437285.1	c.966C>T	p.Ser322Ser	synonymous_variant	Exon 3 of 3		NP_001424214.1
POMGNT2	XM_011534163.3	c.966C>T	p.Ser322Ser	synonymous_variant	Exon 3 of 3		XP_011532465.1
POMGNT2	XM_017007353.2	c.966C>T	p.Ser322Ser	synonymous_variant	Exon 4 of 4		XP_016862842.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POMGNT2	ENST00000344697.3	c.966C>T	p.Ser322Ser	synonymous_variant	Exon 2 of 2	1	NM_032806.6	ENSP00000344125.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	5.7
DANN	Benign	0.59
PhyloP100		1.5

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: rs141319921; hg19: chr3-43121958; COSMIC: COSV104655079;