18-62045910-C-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_176787.5(PIGN):​c.2742G>T​(p.Leu914Leu) 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Consequence

PIGN
NM_176787.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.135
Variant links:
Genes affected
PIGN (HGNC:8967): (phosphatidylinositol glycan anchor biosynthesis class N) This gene encodes a protein that is involved in glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The GPI-anchor is a glycolipid found on many blood cells and serves to anchor proteins to the cell surface. This protein is expressed in the endoplasmic reticulum and transfers phosphoethanolamine (EtNP) to the first mannose of the GPI anchor. Two alternatively spliced variants, which encode an identical isoform, have been reported. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.31).
BP6
Variant 18-62045910-C-A is Benign according to our data. Variant chr18-62045910-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2801929.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.135 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PIGNNM_176787.5 linkc.2742G>T p.Leu914Leu synonymous_variant Exon 31 of 31 ENST00000640252.2 NP_789744.1 O95427A0A024R2C3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PIGNENST00000640252.2 linkc.2742G>T p.Leu914Leu synonymous_variant Exon 31 of 31 1 NM_176787.5 ENSP00000492233.1 O95427
PIGNENST00000400334.7 linkc.2742G>T p.Leu914Leu synonymous_variant Exon 30 of 30 1 ENSP00000383188.2 O95427
PIGNENST00000638424.1 linkn.*710G>T non_coding_transcript_exon_variant Exon 29 of 29 5 ENSP00000491963.1 A0A1W2PQZ1
PIGNENST00000638424.1 linkn.*710G>T 3_prime_UTR_variant Exon 29 of 29 5 ENSP00000491963.1 A0A1W2PQZ1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Multiple congenital anomalies-hypotonia-seizures syndrome 1 Benign:1
Jun 04, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.31
CADD
Benign
5.3
DANN
Benign
0.74

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: chr18-59713143; API