rs3742290

Variant names:

• chr13-52029105-A-G
• rs3742290
• NM_021645.6:c.301A>G

Variant summary

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

The NM_021645.6(UTP14C):​c.301A>G​(p.Thr101Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,614,132 control chromosomes in the GnomAD database, including 11,325 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (811 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10514 hom.)
• Consequence: UTP14C NM_021645.6 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.590
• Publications: 42 publications found

Genes affected

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]

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]

ALG11 Gene-Disease associations (from GenCC):

• ALG11-congenital disorder of glycosylation

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.001627624).
• BP6: Variant 13-52029105-A-G is Benign according to our data. Variant chr13-52029105-A-G is described in ClinVar as Benign. ClinVar VariationId is 312423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021645.6. 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
	UTP14C	NM_021645.6	MANE Select	c.301A>G	p.Thr101Ala	missense	Exon 2 of 2	NP_067677.4
	ALG11	NM_001004127.3	MANE Select	c.*515A>G		3_prime_UTR	Exon 4 of 4	NP_001004127.2	Q2TAA5
	ALG11	NR_036571.3		n.852A>G		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UTP14C	ENST00000521776.2	TSL:1 MANE Select	c.301A>G	p.Thr101Ala	missense	Exon 2 of 2	ENSP00000428619.1	Q5TAP6
	ALG11	ENST00000521508.2	TSL:1 MANE Select	c.*515A>G		3_prime_UTR	Exon 4 of 4	ENSP00000430236.1	Q2TAA5
	ALG11	ENST00000649340.2		c.*515A>G		3_prime_UTR	Exon 4 of 4	ENSP00000497184.2	A0A3B3IS90

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15709 AN: 152136 Hom.: 811 Cov.: 32

Gnomad AFR AF: 0.0613

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.0621

Gnomad SAS AF: 0.0855

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.116

GnomAD2 exomes AF: 0.111 AC: 27943 AN: 251436 AF XY: 0.112

Gnomad AFR exome AF: 0.0615

Gnomad AMR exome AF: 0.117

Gnomad ASJ exome AF: 0.117

Gnomad EAS exome AF: 0.0693

Gnomad FIN exome AF: 0.113

Gnomad NFE exome AF: 0.128

Gnomad OTH exome AF: 0.129

GnomAD4 exome AF: 0.117 AC: 170743 AN: 1461878 Hom.: 10514 Cov.: 106 AF XY: 0.116 AC XY: 84512 AN XY: 727244

African (AFR) AF: 0.0600 AC: 2009 AN: 33480

American (AMR) AF: 0.116 AC: 5193 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 3175 AN: 26136

East Asian (EAS) AF: 0.0518 AC: 2055 AN: 39700

South Asian (SAS) AF: 0.0890 AC: 7676 AN: 86258

European-Finnish (FIN) AF: 0.118 AC: 6297 AN: 53418

Middle Eastern (MID) AF: 0.158 AC: 911 AN: 5768

European-Non Finnish (NFE) AF: 0.123 AC: 136527 AN: 1112000

Other (OTH) AF: 0.114 AC: 6900 AN: 60396

GnomAD4 genome AF: 0.103 AC: 15719 AN: 152254 Hom.: 811 Cov.: 32 AF XY: 0.103 AC XY: 7653 AN XY: 74432

African (AFR) AF: 0.0613 AC: 2548 AN: 41554

American (AMR) AF: 0.123 AC: 1883 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 432 AN: 3472

East Asian (EAS) AF: 0.0622 AC: 323 AN: 5190

South Asian (SAS) AF: 0.0853 AC: 412 AN: 4828

European-Finnish (FIN) AF: 0.122 AC: 1297 AN: 10592

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8387 AN: 68002

Other (OTH) AF: 0.114 AC: 242 AN: 2116

Alfa AF: 0.116 Hom.: 3466

Bravo AF: 0.104

TwinsUK AF: 0.127 AC: 471

ALSPAC AF: 0.117 AC: 451

ESP6500AA AF: 0.0631 AC: 278

ESP6500EA AF: 0.119 AC: 1023

ExAC AF: 0.112 AC: 13594

Asia WGS AF: 0.0680 AC: 237 AN: 3478

EpiCase AF: 0.128

EpiControl AF: 0.131

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.35
DANN	Benign	0.82
DEOGEN2	Benign	0.0024	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.059	N
LIST_S2	Benign	0.71	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.020	N
PhyloP100		-0.59
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.011
Sift	Benign	0.79	T
Sift4G	Benign	0.83	T
Polyphen		0.0040	B
Vest4		0.024
MPC		0.078
ClinPred		0.0032	T
GERP RS		0.15
Varity_R		0.028
gMVP		0.050
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: rs3742290; hg19: chr13-52603241; COSMIC: COSV73000566; COSMIC: COSV73000566;