X-48903516-C-T

Variant names:

• chrX-48903516-C-T
• rs2239453
• ENST00000376521.6:c.*1211G>A

Variant summary

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

The NM_001282651.2(SLC35A2):​c.*1211G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 563,315 control chromosomes in the GnomAD database, including 32,580 homozygotes. There are 82,019 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (6467 hom., 13117 hem., cov: 23)
  • Exomes 𝑓: 0.42 (26113 hom. 68902 hem.)
• Consequence: SLC35A2 NM_001282651.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.433
• Publications: 6 publications found

Genes affected

SLC35A2 (HGNC:11022): (solute carrier family 35 member A2) This gene encodes a member of the nucleotide-sugar transporter family. The encoded protein is a multi-pass membrane protein. It transports UDP-galactose from the cytosol into Golgi vesicles, where it serves as a glycosyl donor for the generation of glycans. Mutations in this gene cause congenital disorder of glycosylation type IIm (CDG2M). Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Oct 2014]

PQBP1 (HGNC:9330): (polyglutamine binding protein 1) This gene encodes a nuclear polyglutamine-binding protein that is involved with transcription activation. The encoded protein contains a WW domain. Mutations in this gene have been found in patients with Renpenning syndrome 1 and other syndromes with X-linked cognitive disability. Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene.[provided by RefSeq, Nov 2009]

PQBP1 Gene-Disease associations (from GenCC):

• Renpenning syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hamel cerebro-palato-cardiac syndrome

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
• X-linked intellectual disability, Golabi-Ito-hall type

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
• X-linked intellectual disability, Porteous type

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
• X-linked intellectual disability, Sutherland-Haan type

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant X-48903516-C-T is Benign according to our data. Variant chrX-48903516-C-T is described in ClinVar as Benign. ClinVar VariationId is 1245601.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282651.2. 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
	SLC35A2	NM_005660.3	MANE Select	c.1164-51G>A		intron	N/A	NP_005651.1	P78381-1
	SLC35A2	NM_001282651.2		c.*1211G>A		3_prime_UTR	Exon 5 of 5	NP_001269580.1	P78381-4
	SLC35A2	NM_001282650.2		c.*1211G>A		3_prime_UTR	Exon 4 of 4	NP_001269579.1	B4DE15

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35A2	ENST00000376521.6	TSL:1	c.*1211G>A		3_prime_UTR	Exon 4 of 4	ENSP00000365704.1	P78381-2
	SLC35A2	ENST00000247138.11	TSL:1 MANE Select	c.1164-51G>A		intron	N/A	ENSP00000247138.5	P78381-1
	PQBP1	ENST00000875808.1		c.*432C>T		3_prime_UTR	Exon 7 of 7	ENSP00000545867.1

Frequencies

GnomAD3 genomes AF: 0.405 AC: 44632 AN: 110316 Hom.: 6466 Cov.: 23

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.724

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.401

GnomAD2 exomes AF: 0.416 AC: 66787 AN: 160412 AF XY: 0.418

Gnomad AFR exome AF: 0.377

Gnomad AMR exome AF: 0.352

Gnomad ASJ exome AF: 0.374

Gnomad EAS exome AF: 0.619

Gnomad FIN exome AF: 0.425

Gnomad NFE exome AF: 0.418

Gnomad OTH exome AF: 0.419

GnomAD4 exome AF: 0.421 AC: 190711 AN: 452946 Hom.: 26113 Cov.: 5 AF XY: 0.424 AC XY: 68902 AN XY: 162638

African (AFR) AF: 0.371 AC: 5190 AN: 13979

American (AMR) AF: 0.356 AC: 11707 AN: 32923

Ashkenazi Jewish (ASJ) AF: 0.377 AC: 5699 AN: 15107

East Asian (EAS) AF: 0.622 AC: 16783 AN: 26980

South Asian (SAS) AF: 0.397 AC: 16012 AN: 40347

European-Finnish (FIN) AF: 0.425 AC: 16815 AN: 39519

Middle Eastern (MID) AF: 0.407 AC: 1227 AN: 3017

European-Non Finnish (NFE) AF: 0.417 AC: 106844 AN: 256311

Other (OTH) AF: 0.421 AC: 10434 AN: 24763

GnomAD4 genome AF: 0.404 AC: 44642 AN: 110369 Hom.: 6467 Cov.: 23 AF XY: 0.402 AC XY: 13117 AN XY: 32661

African (AFR) AF: 0.375 AC: 11392 AN: 30397

American (AMR) AF: 0.389 AC: 4048 AN: 10410

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 967 AN: 2633

East Asian (EAS) AF: 0.599 AC: 2087 AN: 3487

South Asian (SAS) AF: 0.406 AC: 1051 AN: 2586

European-Finnish (FIN) AF: 0.406 AC: 2383 AN: 5869

Middle Eastern (MID) AF: 0.389 AC: 84 AN: 216

European-Non Finnish (NFE) AF: 0.410 AC: 21553 AN: 52608

Other (OTH) AF: 0.397 AC: 595 AN: 1497

Alfa AF: 0.406 Hom.: 36645

Bravo AF: 0.406

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	11
DANN	Benign	0.64
PhyloP100		0.43
Mutation Taster		=100/0	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: rs2239453; hg19: chrX-48760793; COSMIC: COSV54430205; COSMIC: COSV54430205;