rs6558295

Variant names:

• chr8-144084619-C-G
• rs6558295
• NM_003801.4:c.1010+10C>G

Your query was ambiguous. Multiple possible variants found:

• chr8-144084619-C-G
• chr8-144084619-C-T

Variant summary

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

The NM_003801.4(GPAA1):​c.1010+10C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0886 in 1,607,866 control chromosomes in the GnomAD database, including 8,725 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (2291 hom., cov: 33)
  • Exomes 𝑓: 0.083 (6434 hom.)
• Consequence: GPAA1 NM_003801.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.123
• Publications: 33 publications found

Genes affected

GPAA1 (HGNC:4446): (glycosylphosphatidylinositol anchor attachment 1) Posttranslational glycosylphosphatidylinositol (GPI) anchor attachment serves as a general mechanism for linking proteins to the cell surface membrane. The protein encoded by this gene presumably functions in GPI anchoring at the GPI transfer step. The mRNA transcript is ubiquitously expressed in both fetal and adult tissues. The anchor attachment protein 1 contains an N-terminal signal sequence, 1 cAMP- and cGMP-dependent protein kinase phosphorylation site, 1 leucine zipper pattern, 2 potential N-glycosylation sites, and 8 putative transmembrane domains. [provided by RefSeq, Jul 2008]

GPAA1 Gene-Disease associations (from GenCC):

• glycosylphosphatidylinositol biosynthesis defect 15

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 8-144084619-C-G is Benign according to our data. Variant chr8-144084619-C-G is described in ClinVar as Benign. ClinVar VariationId is 1300876.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPAA1	NM_003801.4	c.1010+10C>G		intron_variant	Intron 7 of 11	ENST00000355091.9	NP_003792.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPAA1	ENST00000355091.9	c.1010+10C>G		intron_variant	Intron 7 of 11	1	NM_003801.4	ENSP00000347206.4

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20977 AN: 152132 Hom.: 2283 Cov.: 33

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0877

Gnomad ASJ AF: 0.0778

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.0414

Gnomad FIN AF: 0.0707

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0819

Gnomad OTH AF: 0.125

GnomAD2 exomes AF: 0.0809 AC: 20034 AN: 247792 AF XY: 0.0763

Gnomad AFR exome AF: 0.316

Gnomad AMR exome AF: 0.0537

Gnomad ASJ exome AF: 0.0766

Gnomad EAS exome AF: 0.00601

Gnomad FIN exome AF: 0.0749

Gnomad NFE exome AF: 0.0818

Gnomad OTH exome AF: 0.0786

GnomAD4 exome AF: 0.0834 AC: 121364 AN: 1455616 Hom.: 6434 Cov.: 33 AF XY: 0.0813 AC XY: 58765 AN XY: 723232

African (AFR) AF: 0.320 AC: 10668 AN: 33318

American (AMR) AF: 0.0567 AC: 2529 AN: 44564

Ashkenazi Jewish (ASJ) AF: 0.0737 AC: 1915 AN: 25984

East Asian (EAS) AF: 0.00415 AC: 164 AN: 39522

South Asian (SAS) AF: 0.0400 AC: 3441 AN: 86056

European-Finnish (FIN) AF: 0.0746 AC: 3962 AN: 53124

Middle Eastern (MID) AF: 0.101 AC: 581 AN: 5752

European-Non Finnish (NFE) AF: 0.0838 AC: 92795 AN: 1107196

Other (OTH) AF: 0.0883 AC: 5309 AN: 60100

GnomAD4 genome AF: 0.138 AC: 21020 AN: 152250 Hom.: 2291 Cov.: 33 AF XY: 0.134 AC XY: 9994 AN XY: 74440

African (AFR) AF: 0.302 AC: 12524 AN: 41510

American (AMR) AF: 0.0876 AC: 1340 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0778 AC: 270 AN: 3472

East Asian (EAS) AF: 0.00289 AC: 15 AN: 5182

South Asian (SAS) AF: 0.0420 AC: 203 AN: 4832

European-Finnish (FIN) AF: 0.0707 AC: 751 AN: 10622

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0819 AC: 5567 AN: 68014

Other (OTH) AF: 0.123 AC: 260 AN: 2112

Alfa AF: 0.103 Hom.: 237

Bravo AF: 0.148

Asia WGS AF: 0.0380 AC: 134 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 21, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.2
DANN	Benign	0.59
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs6558295; hg19: chr8-145139522; COSMIC: COSV60155456; COSMIC: COSV60155456;