rs764984

Variant names:

• chr17-16313674-G-C
• rs764984
• NM_004278.4:c.494+60G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-16313674-G-C
• chr17-16313674-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004278.4(PIGL):​c.494+60G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0328 in 1,302,380 control chromosomes in the GnomAD database, including 901 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.047 (205 hom., cov: 33)
  • Exomes 𝑓: 0.031 (696 hom.)
• Consequence: PIGL NM_004278.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.245
• Publications: 5 publications found

Genes affected

PIGL (HGNC:8966): (phosphatidylinositol glycan anchor biosynthesis class L) This gene encodes an enzyme that catalyzes the second step of glycosylphosphatidylinositol (GPI) biosynthesis, which is the de-N-acetylation of N-acetylglucosaminylphosphatidylinositol (GlcNAc-PI). Study of a similar rat enzyme suggests that this protein localizes to the endoplasmic reticulum. [provided by RefSeq, Jul 2008]

PIGL Gene-Disease associations (from GenCC):

• CHIME syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Orphanet, PanelApp Australia
• syndromic intellectual disability

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hyperphosphatasia-intellectual disability syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 17-16313674-G-C is Benign according to our data. Variant chr17-16313674-G-C is described in ClinVar as Benign. ClinVar VariationId is 1262840.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGL	NM_004278.4	c.494+60G>C		intron_variant	Intron 4 of 6	ENST00000225609.10	NP_004269.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGL	ENST00000225609.10	c.494+60G>C		intron_variant	Intron 4 of 6	1	NM_004278.4	ENSP00000225609.5

Frequencies

GnomAD3 genomes AF: 0.0469 AC: 7134 AN: 152046 Hom.: 206 Cov.: 33

Gnomad AFR AF: 0.0850

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0446

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.0623

Gnomad SAS AF: 0.0431

Gnomad FIN AF: 0.0395

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0261

Gnomad OTH AF: 0.0517

GnomAD4 exome AF: 0.0309 AC: 35583 AN: 1150216 Hom.: 696 AF XY: 0.0310 AC XY: 18099 AN XY: 584750

African (AFR) AF: 0.0867 AC: 2378 AN: 27422

American (AMR) AF: 0.0482 AC: 2130 AN: 44166

Ashkenazi Jewish (ASJ) AF: 0.0284 AC: 685 AN: 24142

East Asian (EAS) AF: 0.0446 AC: 1697 AN: 38056

South Asian (SAS) AF: 0.0430 AC: 3441 AN: 79982

European-Finnish (FIN) AF: 0.0389 AC: 2067 AN: 53182

Middle Eastern (MID) AF: 0.0400 AC: 203 AN: 5070

European-Non Finnish (NFE) AF: 0.0254 AC: 21078 AN: 828254

Other (OTH) AF: 0.0381 AC: 1904 AN: 49942

GnomAD4 genome AF: 0.0469 AC: 7137 AN: 152164 Hom.: 205 Cov.: 33 AF XY: 0.0465 AC XY: 3461 AN XY: 74396

African (AFR) AF: 0.0848 AC: 3519 AN: 41494

American (AMR) AF: 0.0446 AC: 682 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0268 AC: 93 AN: 3466

East Asian (EAS) AF: 0.0623 AC: 323 AN: 5186

South Asian (SAS) AF: 0.0433 AC: 209 AN: 4824

European-Finnish (FIN) AF: 0.0395 AC: 418 AN: 10590

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0262 AC: 1779 AN: 68010

Other (OTH) AF: 0.0507 AC: 107 AN: 2110

Alfa AF: 0.00820 Hom.: 3

Bravo AF: 0.0494

Asia WGS AF: 0.0490 AC: 173 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 17, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.0
DANN	Benign	0.54
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

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: rs764984; hg19: chr17-16216988; COSMIC: COSV107309128; COSMIC: COSV107309128;