Variant 2-219501550-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_013335.4(GMPPA):c.213C>T(p.Ala71=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 1,611,450 control chromosomes in the GnomAD database, including 230 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 16 hom., cov: 32)

Exomes 𝑓: 0.014 ( 214 hom. )

Consequence

GMPPA
NM_013335.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.387

Variant links:

Genes affected

GMPPA (HGNC:22923): (GDP-mannose pyrophosphorylase A) This gene is thought to encode a GDP-mannose pyrophosphorylase. This enzyme catalyzes the reaction which converts mannose-1-phosphate and GTP to GDP-mannose which is involved in the production of N-linked oligosaccharides. [provided by RefSeq, Jul 2008]

GMPPA links:

ASIC4-AS1 (HGNC:40960): (ASIC4 antisense RNA 1)

ASIC4-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 2-219501550-C-T is Benign according to our data. Variant chr2-219501550-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 382083.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.387 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0117 (1779/152260) while in subpopulation NFE AF= 0.0176 (1195/68026). AF 95% confidence interval is 0.0167. There are 16 homozygotes in gnomad4. There are 900 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GMPPA	NM_013335.4 linkuse as main transcript	c.213C>T	p.Ala71=	synonymous_variant	4/13	ENST00000313597.10
ASIC4-AS1	XR_923921.2 linkuse as main transcript	n.391+15146G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GMPPA	ENST00000313597.10 linkuse as main transcript	c.213C>T	p.Ala71=	synonymous_variant	4/13	1	NM_013335.4	P1	Q96IJ6-1
ASIC4-AS1	ENST00000429882.1 linkuse as main transcript	n.182+15146G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0117

AC:

1779

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00222

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.0124

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.0366

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0176

Gnomad OTH

AF:

0.00622

GnomAD3 exomes

AF:

0.0123

AC:

3091

AN:

251472

Hom.:

AF XY:

0.0123

AC XY:

1671

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.00154

Gnomad AMR exome

AF:

0.00301

Gnomad ASJ exome

AF:

0.0118

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00477

Gnomad FIN exome

AF:

0.0331

Gnomad NFE exome

AF:

0.0168

Gnomad OTH exome

AF:

0.0106

GnomAD4 exome

AF:

0.0142

AC:

20750

AN:

1459190

Hom.:

214

Cov.:

AF XY:

0.0140

AC XY:

10133

AN XY:

726118

show subpopulations

Gnomad4 AFR exome

AF:

0.00212

Gnomad4 AMR exome

AF:

0.00295

Gnomad4 ASJ exome

AF:

0.0118

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00515

Gnomad4 FIN exome

AF:

0.0369

Gnomad4 NFE exome

AF:

0.0154

Gnomad4 OTH exome

AF:

0.0113

GnomAD4 genome

AF:

0.0117

AC:

1779

AN:

152260

Hom.:

Cov.:

AF XY:

0.0121

AC XY:

900

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00222

Gnomad4 AMR

AF:

0.00242

Gnomad4 ASJ

AF:

0.0124

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.0366

Gnomad4 NFE

AF:

0.0176

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.0149

Hom.:

Bravo

AF:

0.00804

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0129

EpiControl

AF:

0.0129

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Alacrima, achalasia, and intellectual disability syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Nov 16, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 29, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

5.6

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over