chr20-45416168-T-C

Variant names:

• chr20-45416168-T-C
• rs371353348
• NM_015937.6:c.12T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_015937.6(PIGT):​c.12T>C​(p.Ala4Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000291 in 1,568,838 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0016 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00015 (3 hom.)
• Consequence: PIGT NM_015937.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -5.20
• 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: ClinGen, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), G2P

LOC107985405 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 20-45416168-T-C is Benign according to our data. Variant chr20-45416168-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 741217.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.2 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00159 (242/152368) while in subpopulation AFR AF = 0.00563 (234/41600). AF 95% confidence interval is 0.00503. There are 3 homozygotes in GnomAd4. There are 117 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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.12T>C	p.Ala4Ala	synonymous	Exon 1 of 12	NP_057021.2
	PIGT	NM_001184728.3		c.12T>C	p.Ala4Ala	synonymous	Exon 1 of 11	NP_001171657.1	Q969N2-5
	PIGT	NM_001184729.3		c.12T>C	p.Ala4Ala	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.12T>C	p.Ala4Ala	synonymous	Exon 1 of 12	ENSP00000279036.6	Q969N2-1
	PIGT	ENST00000372689.9	TSL:1	c.12T>C	p.Ala4Ala	synonymous	Exon 1 of 11	ENSP00000361774.4	Q969N2-6
	PIGT	ENST00000639382.1	TSL:1	c.12T>C	p.Ala4Ala	synonymous	Exon 1 of 9	ENSP00000491534.1	A0A1W2PPQ7

Frequencies

GnomAD3 genomes AF: 0.00160 AC: 243 AN: 152250 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00567

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

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: 0.000956

GnomAD2 exomes AF: 0.000317 AC: 56 AN: 176830 AF XY: 0.000301

Gnomad AFR exome AF: 0.00509

Gnomad AMR exome AF: 0.000292

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: 0.000214

GnomAD4 exome AF: 0.000151 AC: 214 AN: 1416470 Hom.: 3 Cov.: 31 AF XY: 0.000130 AC XY: 91 AN XY: 701156

African (AFR) AF: 0.00494 AC: 159 AN: 32168

American (AMR) AF: 0.000417 AC: 16 AN: 38400

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25332

East Asian (EAS) AF: 0.00 AC: 0 AN: 36740

South Asian (SAS) AF: 0.0000123 AC: 1 AN: 81192

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48648

Middle Eastern (MID) AF: 0.000228 AC: 1 AN: 4392

European-Non Finnish (NFE) AF: 0.00000550 AC: 6 AN: 1091038

Other (OTH) AF: 0.000529 AC: 31 AN: 58560

GnomAD4 genome AF: 0.00159 AC: 242 AN: 152368 Hom.: 3 Cov.: 33 AF XY: 0.00157 AC XY: 117 AN XY: 74510

African (AFR) AF: 0.00562 AC: 234 AN: 41600

American (AMR) AF: 0.000327 AC: 5 AN: 15308

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68028

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000402 Hom.: 0

Bravo AF: 0.00156

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Multiple congenital anomalies-hypotonia-seizures syndrome 3 (1)
-	-	1	not provided (1)
-	-	1	PIGT-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.1
DANN	Benign	0.66
PhyloP100		-5.2
PromoterAI		0.29	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	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: rs371353348; hg19: chr20-44044808;