rs990693871

Variant names:

• chr13-102789037-T-A
• rs990693871
• NM_024089.3:c.1268A>T

Your query was ambiguous. Multiple possible variants found:

• chr13-102789037-T-A
• chr13-102789037-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024089.3(POGLUT2):​c.1268A>T​(p.Lys423Ile) variant causes a missense change. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K423T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: POGLUT2 NM_024089.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.23
• Publications: 0 publications found

Genes affected

POGLUT2 (HGNC:19350): (protein O-glucosyltransferase 2) This gene encodes a protein product localized to the lumen of the endoplasmic reticulum. As a member of the endoplasmic reticulum protein family the encoded protein contains a Lys-Asp-Glu-Leu or KDEL motif located at the extreme C-terminus which prevents all endoplasmic reticulum resident proteins from being secreted. Proteins carrying this motif are bound by a receptor in the Golgi apparatus so that the receptor-ligand complex returns to the endoplasmic reticulum. A processed non-transcribed pseudogene located in an intron of a sodium transporter gene on chromosome 5 has been defined for this gene. This gene has multiple transcript variants which are predicted to encode distinct isoforms. [provided by RefSeq, Jan 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32623863).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POGLUT2	NM_024089.3	c.1268A>T	p.Lys423Ile	missense_variant	Exon 7 of 10	ENST00000376004.5	NP_076994.2
POGLUT2	NM_001439010.1	c.1268A>T	p.Lys423Ile	missense_variant	Exon 7 of 9		NP_001425939.1
POGLUT2	NM_001318732.2	c.611A>T	p.Lys204Ile	missense_variant	Exon 8 of 11		NP_001305661.1
POGLUT2	XM_047430604.1	c.611A>T	p.Lys204Ile	missense_variant	Exon 5 of 8		XP_047286560.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POGLUT2	ENST00000376004.5	c.1268A>T	p.Lys423Ile	missense_variant	Exon 7 of 10	1	NM_024089.3	ENSP00000365172.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.096	T
Eigen	Benign	-0.0097
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-1.0	T
PhyloP100		4.2
PrimateAI	Benign	0.33	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.11
Sift	Benign	0.044	D
Sift4G	Benign	0.080	T
Polyphen		0.093	B
Vest4		0.52
MutPred		0.48		Loss of disorder (P = 0.0017);
MVP		0.47
MPC		0.34
ClinPred		0.91	D
GERP RS		5.7
Varity_R		0.42
gMVP		0.56
Mutation Taster		=71/29	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: rs990693871; hg19: chr13-103441387;