ENST00000508953.2:n.295G>A

Variant names:

• chr12-148821-C-T
• rs2270797
• ENST00000508953.2:n.295G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000508953.2(ENSG00000249695):​n.295G>A 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 0.084 in 152,112 control chromosomes in the GnomAD database, including 817 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 0.084 (817 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000249695 ENST00000508953.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.318
• Publications: 2 publications found

Genes affected

ENSG00000249695 (HGNC:58418):

IQSEC3 (HGNC:29193): (IQ motif and Sec7 domain ArfGEF 3) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in several processes, including actin cytoskeleton organization; activation of GTPase activity; and regulation of small GTPase mediated signal transduction. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IQSEC3	NM_001170738.2	c.2153+7536C>T		intron_variant	Intron 5 of 13	ENST00000538872.6	NP_001164209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000249695	ENST00000508953.2	n.295G>A		non_coding_transcript_exon_variant	Exon 1 of 7	1
IQSEC3	ENST00000538872.6	c.2153+7536C>T		intron_variant	Intron 5 of 13	5	NM_001170738.2	ENSP00000437554.1
IQSEC3	ENST00000382841.2	c.1244+7536C>T		intron_variant	Intron 4 of 12	2		ENSP00000372292.2
ENSG00000249695	ENST00000505893.6	n.91+258G>A		intron_variant	Intron 1 of 9	2

Frequencies

GnomAD3 genomes AF: 0.0839 AC: 12759 AN: 151994 Hom.: 817 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0488

Gnomad ASJ AF: 0.0426

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.0761

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0418

Gnomad OTH AF: 0.0861

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0840 AC: 12772 AN: 152112 Hom.: 817 Cov.: 32 AF XY: 0.0886 AC XY: 6592 AN XY: 74378

African (AFR) AF: 0.137 AC: 5666 AN: 41434

American (AMR) AF: 0.0484 AC: 741 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0426 AC: 148 AN: 3472

East Asian (EAS) AF: 0.229 AC: 1183 AN: 5158

South Asian (SAS) AF: 0.232 AC: 1115 AN: 4814

European-Finnish (FIN) AF: 0.0761 AC: 807 AN: 10608

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

European-Non Finnish (NFE) AF: 0.0418 AC: 2841 AN: 68012

Other (OTH) AF: 0.0871 AC: 184 AN: 2112

Alfa AF: 0.0557 Hom.: 1500

Bravo AF: 0.0824

Asia WGS AF: 0.237 AC: 824 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.4
DANN	Benign	0.63
PhyloP100		0.32
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: rs2270797; hg19: chr12-257987;