rs61958802

Variant names:

• chr13-52024663-G-A
• rs61958802
• NM_001004127.3:c.933G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001004127.3(ALG11):​c.933G>A​(p.Pro311Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0451 in 1,613,952 control chromosomes in the GnomAD database, including 1,975 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.035 (132 hom., cov: 32)
  • Exomes 𝑓: 0.046 (1843 hom.)
• Consequence: ALG11 NM_001004127.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.95
• Publications: 10 publications found

Genes affected

ALG11 (HGNC:32456): (ALG11 alpha-1,2-mannosyltransferase) This gene encodes a GDP-Man:Man3GlcNAc2-PP-dolichol-alpha1,2-mannosyltransferase which is localized to the cytosolic side of the endoplasmic reticulum (ER) and catalyzes the transfer of the fourth and fifth mannose residue from GDP-mannose (GDP-Man) to Man3GlcNAc2-PP-dolichol and Man4GlcNAc2-PP-dolichol resulting in the production of Man5GlcNAc2-PP-dolichol. Mutations in this gene are associated with congenital disorder of glycosylation type Ip (CDGIP). This gene overlaps but is distinct from the UTP14, U3 small nucleolar ribonucleoprotein, homolog C (yeast) gene. A pseudogene of the GDP-Man:Man3GlcNAc2-PP-dolichol-alpha1,2-mannosyltransferase has been identified on chromosome 19. [provided by RefSeq, Aug 2010]

UTP14C (HGNC:20321): (UTP14C small subunit processome component) Predicted to be involved in several processes, including meiotic cell cycle; rRNA processing; and spermatogenesis. Located in cytosol and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 13-52024663-G-A is Benign according to our data. Variant chr13-52024663-G-A is described in ClinVar as Benign. ClinVar VariationId is 312413.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.95 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.083 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004127.3. 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
	ALG11	NM_001004127.3	MANE Select	c.933G>A	p.Pro311Pro	synonymous	Exon 3 of 4	NP_001004127.2	Q2TAA5
	ALG11	NR_036571.3		n.66-3656G>A		intron	N/A
	UTP14C	NM_021645.6	MANE Select	c.-761G>A		upstream_gene	N/A	NP_067677.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG11	ENST00000521508.2	TSL:1 MANE Select	c.933G>A	p.Pro311Pro	synonymous	Exon 3 of 4	ENSP00000430236.1	Q2TAA5
	ALG11	ENST00000649340.2		c.933G>A	p.Pro311Pro	synonymous	Exon 3 of 4	ENSP00000497184.2	A0A3B3IS90
	ALG11	ENST00000681053.1		c.702G>A	p.Pro234Pro	synonymous	Exon 2 of 3	ENSP00000505307.1	A0A7P0T8Y4

Frequencies

GnomAD3 genomes AF: 0.0346 AC: 5265 AN: 152148 Hom.: 130 Cov.: 32

Gnomad AFR AF: 0.0131

Gnomad AMI AF: 0.0198

Gnomad AMR AF: 0.0288

Gnomad ASJ AF: 0.0521

Gnomad EAS AF: 0.00961

Gnomad SAS AF: 0.0899

Gnomad FIN AF: 0.0284

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0469

Gnomad OTH AF: 0.0417

GnomAD2 exomes AF: 0.0425 AC: 10655 AN: 250920 AF XY: 0.0473

Gnomad AFR exome AF: 0.0111

Gnomad AMR exome AF: 0.0212

Gnomad ASJ exome AF: 0.0531

Gnomad EAS exome AF: 0.00877

Gnomad FIN exome AF: 0.0317

Gnomad NFE exome AF: 0.0475

Gnomad OTH exome AF: 0.0448

GnomAD4 exome AF: 0.0462 AC: 67528 AN: 1461686 Hom.: 1843 Cov.: 32 AF XY: 0.0479 AC XY: 34845 AN XY: 727126

African (AFR) AF: 0.0119 AC: 397 AN: 33474

American (AMR) AF: 0.0210 AC: 939 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.0512 AC: 1338 AN: 26132

East Asian (EAS) AF: 0.00857 AC: 340 AN: 39692

South Asian (SAS) AF: 0.0900 AC: 7759 AN: 86232

European-Finnish (FIN) AF: 0.0310 AC: 1657 AN: 53408

Middle Eastern (MID) AF: 0.0771 AC: 445 AN: 5768

European-Non Finnish (NFE) AF: 0.0467 AC: 51889 AN: 1111892

Other (OTH) AF: 0.0458 AC: 2764 AN: 60382

GnomAD4 genome AF: 0.0346 AC: 5269 AN: 152266 Hom.: 132 Cov.: 32 AF XY: 0.0347 AC XY: 2581 AN XY: 74432

African (AFR) AF: 0.0131 AC: 544 AN: 41562

American (AMR) AF: 0.0287 AC: 439 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0521 AC: 181 AN: 3472

East Asian (EAS) AF: 0.00963 AC: 50 AN: 5190

South Asian (SAS) AF: 0.0900 AC: 434 AN: 4824

European-Finnish (FIN) AF: 0.0284 AC: 301 AN: 10604

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0469 AC: 3189 AN: 68012

Other (OTH) AF: 0.0450 AC: 95 AN: 2110

Alfa AF: 0.0415 Hom.: 82

Bravo AF: 0.0315

Asia WGS AF: 0.0640 AC: 221 AN: 3478

EpiCase AF: 0.0505

EpiControl AF: 0.0518

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	ALG11-congenital disorder of glycosylation (2)
-	-	2	not specified (2)
-	-	1	ALG11-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	12
DANN	Benign	0.70
PhyloP100		-1.9
PromoterAI		-0.091	Neutral
Mutation Taster		=99/1	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: rs61958802; hg19: chr13-52598799;