chr14-67599842-A-T

Variant names:

• chr14-67599842-A-T
• rs2295644
• NM_004569.5:c.180+182T>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004569.5(PIGH):​c.180+182T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 151,966 control chromosomes in the GnomAD database, including 12,487 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (12487 hom., cov: 31)
• Consequence: PIGH NM_004569.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14

Genes affected

PIGH (HGNC:8964): (phosphatidylinositol glycan anchor biosynthesis class H) This gene encodes an endoplasmic reticulum associated protein that is involved in glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The GPI anchor is a glycolipid found on many blood cells and which serves to anchor proteins to the cell surface. The protein encoded by this gene is a subunit of the GPI N-acetylglucosaminyl (GlcNAc) transferase that transfers GlcNAc to phosphatidylinositol (PI) on the cytoplasmic side of the endoplasmic reticulum. [provided by RefSeq, Jul 2008]

GPHN (HGNC:15465): (gephyrin) This gene encodes a neuronal assembly protein that anchors inhibitory neurotransmitter receptors to the postsynaptic cytoskeleton via high affinity binding to a receptor subunit domain and tubulin dimers. In nonneuronal tissues, the encoded protein is also required for molybdenum cofactor biosynthesis. Mutations in this gene may be associated with the neurological condition hyperplexia and also lead to molybdenum cofactor deficiency. Numerous alternatively spliced transcript variants encoding different isoforms have been described; however, the full-length nature of all transcript variants is not currently known. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGH	NM_004569.5	c.180+182T>A		intron_variant	Intron 1 of 3	ENST00000216452.9	NP_004560.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGH	ENST00000216452.9	c.180+182T>A		intron_variant	Intron 1 of 3	1	NM_004569.5	ENSP00000216452.4

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60795 AN: 151850 Hom.: 12487 Cov.: 31

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.550

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.382

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.400 AC: 60810 AN: 151966 Hom.: 12487 Cov.: 31 AF XY: 0.401 AC XY: 29754 AN XY: 74258

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.522

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.470

Gnomad4 NFE AF: 0.434

Gnomad4 OTH AF: 0.383

Alfa AF: 0.406 Hom.: 1545

Bravo AF: 0.390

Asia WGS AF: 0.391 AC: 1358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.5
DANN	Benign	0.59

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

LitVar

Other links and lift over

dbSNP: rs2295644; hg19: chr14-68066559; COSMIC: COSV53615395;