rs2282538

Variant names:

• chr11-62832260-C-T
• rs2282538
• ENST00000535817.2:n.27C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4 BA1

The ENST00000535817.2(STX5-DT):​n.27C>T 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 0.0687 in 596,750 control chromosomes in the GnomAD database, including 1,775 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.071 (417 hom., cov: 31)
  • Exomes 𝑓: 0.068 (1358 hom.)
• Consequence: STX5-DT ENST00000535817.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.57
• Publications: 5 publications found

Genes affected

STX5-DT (HGNC:55488): (STX5 divergent transcript)

STX5 (HGNC:11440): (syntaxin 5) This gene encodes a member of the syntaxin or t-SNARE (target-SNAP receptor) family. These proteins are found on cell membranes and serve as the targets for v-SNAREs (vesicle-SNAP receptors), permitting specific synaptic vesicle docking and fusion. The encoded protein regulates endoplasmic reticulum to Golgi transport and plays a critical role in autophagy. Autoantibodies targeting the encoded protein may be a diagnostic marker for endometriosis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2011]

TEX54 (HGNC:53729): (testis expressed 54)

WDR74 (HGNC:25529): (WD repeat domain 74) Involved in rRNA processing and ribosomal large subunit biogenesis. Located in nucleoplasm. Colocalizes with nuclear exosome (RNase complex) and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.15).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000535817.2. 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
	STX5-DT	NR_135084.1		n.27C>T		non_coding_transcript_exon	Exon 1 of 2
	STX5	NM_003164.5	MANE Select	c.-326G>A		upstream_gene	N/A	NP_003155.2	Q13190-1
	TEX54	NM_001395459.1	MANE Select	c.*116G>A		downstream_gene	N/A	NP_001382388.1	A0A1B0GVG6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STX5-DT	ENST00000535817.2	TSL:3	n.27C>T		non_coding_transcript_exon	Exon 1 of 2
	STX5-DT	ENST00000741088.1		n.17C>T		non_coding_transcript_exon	Exon 1 of 3
	STX5	ENST00000294179.8	TSL:1 MANE Select	c.-326G>A		upstream_gene	N/A	ENSP00000294179.3	Q13190-1

Frequencies

GnomAD3 genomes AF: 0.0708 AC: 10763 AN: 152042 Hom.: 418 Cov.: 31

Gnomad AFR AF: 0.0914

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0432

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.0754

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0531

Gnomad OTH AF: 0.0651

GnomAD4 exome AF: 0.0679 AC: 30200 AN: 444590 Hom.: 1358 Cov.: 0 AF XY: 0.0702 AC XY: 16411 AN XY: 233748

African (AFR) AF: 0.0910 AC: 1119 AN: 12294

American (AMR) AF: 0.0343 AC: 634 AN: 18500

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 1902 AN: 13656

East Asian (EAS) AF: 0.154 AC: 4770 AN: 30916

South Asian (SAS) AF: 0.0937 AC: 4255 AN: 45406

European-Finnish (FIN) AF: 0.0686 AC: 2021 AN: 29460

Middle Eastern (MID) AF: 0.0779 AC: 152 AN: 1950

European-Non Finnish (NFE) AF: 0.0512 AC: 13656 AN: 266606

Other (OTH) AF: 0.0655 AC: 1691 AN: 25802

GnomAD4 genome AF: 0.0709 AC: 10786 AN: 152160 Hom.: 417 Cov.: 31 AF XY: 0.0730 AC XY: 5432 AN XY: 74394

African (AFR) AF: 0.0915 AC: 3799 AN: 41514

American (AMR) AF: 0.0432 AC: 661 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 470 AN: 3470

East Asian (EAS) AF: 0.146 AC: 751 AN: 5146

South Asian (SAS) AF: 0.107 AC: 517 AN: 4814

European-Finnish (FIN) AF: 0.0754 AC: 800 AN: 10604

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0531 AC: 3610 AN: 68010

Other (OTH) AF: 0.0696 AC: 147 AN: 2112

Alfa AF: 0.0658 Hom.: 65

Bravo AF: 0.0682

Asia WGS AF: 0.114 AC: 394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.15
CADD	Benign	18
DANN	Benign	0.94
PhyloP100		3.6
PromoterAI		-0.11	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2282538;

hg19: chr11-62599732;