NM_017739.4:c.1980A>G

Variant names:

• chr1-46189273-T-C
• NM_017739.4:c.1980A>G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_017739.4(POMGNT1):​c.1980A>G​(p.Thr660Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,106 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. T660T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: POMGNT1 NM_017739.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.570

Genes affected

POMGNT1 (HGNC:19139): (protein O-linked mannose N-acetylglucosaminyltransferase 1 (beta 1,2-)) This gene encodes a type II transmembrane protein that resides in the Golgi apparatus. It participates in O-mannosyl glycosylation and is specific for alpha linked terminal mannose. Mutations in this gene may be associated with muscle-eye-brain disease and several congenital muscular dystrophies. Alternatively spliced transcript variants that encode different protein isoforms have been described. [provided by RefSeq, Feb 2014]

TSPAN1 (HGNC:20657): (tetraspanin 1) The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08446273).
• BP7: Synonymous conserved (PhyloP=-0.57 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POMGNT1	NM_017739.4	c.1980A>G	p.Thr660Thr	synonymous_variant	Exon 22 of 22	ENST00000371984.8	NP_060209.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POMGNT1	ENST00000371984.8	c.1980A>G	p.Thr660Thr	synonymous_variant	Exon 22 of 22	1	NM_017739.4	ENSP00000361052.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461106 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726896

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	6.2
DANN	Benign	0.95
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.098
Sift	Benign	0.064	T
Sift4G	Benign	0.15	T
Vest4		0.22
MutPred		0.073		Loss of glycosylation at P654 (P = 0.1537);
MVP		0.24
MPC		0.25
ClinPred		0.30	T
GERP RS		-0.99
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
gMVP		0.56

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-46654945; COSMIC: COSV64340798; COSMIC: COSV64340798;