rs41272703

Variant names:

• chr2-219501550-C-T
• rs41272703
• NM_013335.4:c.213C>T

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_013335.4(GMPPA):​c.213C>T​(p.Ala71Ala) 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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.387
• Publications: 2 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 16 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013335.4. 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
	GMPPA	NM_013335.4	MANE Select	c.213C>T	p.Ala71Ala	synonymous	Exon 4 of 13	NP_037467.2
	GMPPA	NM_001438893.1		c.213C>T	p.Ala71Ala	synonymous	Exon 4 of 12	NP_001425822.1
	GMPPA	NM_001438894.1		c.213C>T	p.Ala71Ala	synonymous	Exon 4 of 12	NP_001425823.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GMPPA	ENST00000313597.10	TSL:1 MANE Select	c.213C>T	p.Ala71Ala	synonymous	Exon 4 of 13	ENSP00000315925.6	Q96IJ6-1
	GMPPA	ENST00000358215.8	TSL:1	c.213C>T	p.Ala71Ala	synonymous	Exon 4 of 13	ENSP00000350949.3	Q96IJ6-1
	GMPPA	ENST00000950500.1		c.213C>T	p.Ala71Ala	synonymous	Exon 4 of 13	ENSP00000620559.1

Frequencies

GnomAD3 genomes AF: 0.0117 AC: 1779 AN: 152142 Hom.: 16 Cov.: 32

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

GnomAD2 exomes AF: 0.0123 AC: 3091 AN: 251472 AF XY: 0.0123

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 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.: 29 AF XY: 0.0140 AC XY: 10133 AN XY: 726118

African (AFR) AF: 0.00212 AC: 71 AN: 33432

American (AMR) AF: 0.00295 AC: 132 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 309 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00515 AC: 444 AN: 86194

European-Finnish (FIN) AF: 0.0369 AC: 1970 AN: 53412

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5762

European-Non Finnish (NFE) AF: 0.0154 AC: 17135 AN: 1109540

Other (OTH) AF: 0.0113 AC: 680 AN: 60330

GnomAD4 genome AF: 0.0117 AC: 1779 AN: 152260 Hom.: 16 Cov.: 32 AF XY: 0.0121 AC XY: 900 AN XY: 74446

African (AFR) AF: 0.00222 AC: 92 AN: 41534

American (AMR) AF: 0.00242 AC: 37 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0124 AC: 43 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4826

European-Finnish (FIN) AF: 0.0366 AC: 388 AN: 10604

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

European-Non Finnish (NFE) AF: 0.0176 AC: 1195 AN: 68026

Other (OTH) AF: 0.00616 AC: 13 AN: 2112

Alfa AF: 0.0146 Hom.: 22

Bravo AF: 0.00804

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0129

EpiControl AF: 0.0129

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Alacrima, achalasia, and intellectual disability syndrome (2)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	5.6
DANN	Benign	0.81
PhyloP100		-0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	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: rs41272703; hg19: chr2-220366272;