rs1041711313

Variant names:

• chr20-45416162-G-A
• rs1041711313
• NM_015937.6:c.6G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-45416162-G-A
• chr20-45416162-G-C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_015937.6(PIGT):​c.6G>A​(p.Ala2Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000384 in 1,561,130 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. A2A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: PIGT NM_015937.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75
• Publications: 0 publications found

Genes affected

PIGT (HGNC:14938): (phosphatidylinositol glycan anchor biosynthesis class T) 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 an essential component of the multisubunit enzyme, GPI transamidase. GPI transamidase mediates GPI anchoring in the endoplasmic reticulum, by catalyzing the transfer of fully assembled GPI units to proteins. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]

PIGT Gene-Disease associations (from GenCC):

• multiple congenital anomalies-hypotonia-seizures syndrome 3

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia, G2P, Orphanet

LOC107985405 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BP7: Synonymous conserved (PhyloP=1.75 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015937.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGT	NM_015937.6	MANE Select	c.6G>A	p.Ala2Ala	synonymous	Exon 1 of 12	NP_057021.2
	PIGT	NM_001184728.3		c.6G>A	p.Ala2Ala	synonymous	Exon 1 of 11	NP_001171657.1	Q969N2-5
	PIGT	NM_001184729.3		c.6G>A	p.Ala2Ala	synonymous	Exon 1 of 11	NP_001171658.1	Q969N2-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGT	ENST00000279036.12	TSL:1 MANE Select	c.6G>A	p.Ala2Ala	synonymous	Exon 1 of 12	ENSP00000279036.6	Q969N2-1
	PIGT	ENST00000372689.9	TSL:1	c.6G>A	p.Ala2Ala	synonymous	Exon 1 of 11	ENSP00000361774.4	Q969N2-6
	PIGT	ENST00000639382.1	TSL:1	c.6G>A	p.Ala2Ala	synonymous	Exon 1 of 9	ENSP00000491534.1	A0A1W2PPQ7

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152244 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 168830 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000355 AC: 5 AN: 1408886 Hom.: 0 Cov.: 31 AF XY: 0.00000431 AC XY: 3 AN XY: 696780

African (AFR) AF: 0.00 AC: 0 AN: 31840

American (AMR) AF: 0.00 AC: 0 AN: 37266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25172

East Asian (EAS) AF: 0.00 AC: 0 AN: 36270

South Asian (SAS) AF: 0.00 AC: 0 AN: 80560

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48060

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4270

European-Non Finnish (NFE) AF: 0.00000460 AC: 5 AN: 1087166

Other (OTH) AF: 0.00 AC: 0 AN: 58282

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152244 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74380

African (AFR) AF: 0.00 AC: 0 AN: 41470

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	13
DANN	Benign	0.94
PhyloP100		1.7
PromoterAI		-0.45	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6

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: rs1041711313; hg19: chr20-44044802;