ENST00000474671.6:n.21A>G

Variant names:

• chrX-48897951-A-G
• rs781841269
• ENST00000474671.6:n.21A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000474671.6(PQBP1):​n.21A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00083 in 864,017 control chromosomes in the GnomAD database, including 3 homozygotes. There are 248 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (1 hom., 70 hem., cov: 24)
  • Exomes 𝑓: 0.00075 (2 hom. 178 hem.)
• Consequence: PQBP1 ENST00000474671.6 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.240
• Publications: 0 publications found

Genes affected

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]

TIMM17B (HGNC:17310): (translocase of inner mitochondrial membrane 17B) This gene encodes a multipass transmembrane protein that forms an integral component of the mitochondrial translocase TIM23 complex. This complex facilitates the transport of mitochondrial proteins from the cytosol across the mitochondrial inner membrane and into the mitochondrion. There is a pseudogene for this gene on chromosome 12. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant X-48897951-A-G is Benign according to our data. Variant chrX-48897951-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1203191.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00138 (154/111949) while in subpopulation NFE AF = 0.000848 (45/53045). AF 95% confidence interval is 0.000651. There are 1 homozygotes in GnomAd4. There are 70 alleles in the male GnomAd4 subpopulation. Median coverage is 24. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 70 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PQBP1	NM_001032382.2	c.-150A>G		5_prime_UTR_variant	Exon 1 of 7	ENST00000447146.7	NP_001027554.1
TIMM17B	NM_001395498.1	c.-202T>C		upstream_gene_variant		ENST00000696123.1	NP_001382427.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PQBP1	ENST00000447146.7	c.-150A>G		5_prime_UTR_variant	Exon 1 of 7	1	NM_001032382.2	ENSP00000391759.2
TIMM17B	ENST00000696123.1	c.-202T>C		upstream_gene_variant			NM_001395498.1	ENSP00000512416.1

Frequencies

GnomAD3 genomes AF: 0.00138 AC: 154 AN: 111893 Hom.: 1 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0179

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000848

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000749 AC: 563 AN: 752068 Hom.: 2 Cov.: 12 AF XY: 0.000988 AC XY: 178 AN XY: 180212

African (AFR) AF: 0.00 AC: 0 AN: 18028

American (AMR) AF: 0.0000639 AC: 1 AN: 15655

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12608

East Asian (EAS) AF: 0.00 AC: 0 AN: 25062

South Asian (SAS) AF: 0.0000283 AC: 1 AN: 35357

European-Finnish (FIN) AF: 0.0137 AC: 309 AN: 22537

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3227

European-Non Finnish (NFE) AF: 0.000387 AC: 227 AN: 585818

Other (OTH) AF: 0.000740 AC: 25 AN: 33776

GnomAD4 genome AF: 0.00138 AC: 154 AN: 111949 Hom.: 1 Cov.: 24 AF XY: 0.00205 AC XY: 70 AN XY: 34173

African (AFR) AF: 0.00 AC: 0 AN: 30856

American (AMR) AF: 0.00 AC: 0 AN: 10626

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2645

East Asian (EAS) AF: 0.00 AC: 0 AN: 3555

South Asian (SAS) AF: 0.00 AC: 0 AN: 2707

European-Finnish (FIN) AF: 0.0179 AC: 109 AN: 6087

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.000848 AC: 45 AN: 53045

Other (OTH) AF: 0.00 AC: 0 AN: 1527

Alfa AF: 0.00167 Hom.: 8

Bravo AF: 0.000283

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 05, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	11
DANN	Benign	0.68
PhyloP100		0.24
PromoterAI		0.063	Neutral
Mutation Taster		=100/0	polymorphism

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: rs781841269; hg19: chrX-48755234;