rs563815894

Variant names:

• chr12-67167-G-A
• rs563815894
• NM_001170738.2:c.285G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-67167-G-A
• chr12-67167-G-C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_001170738.2(IQSEC3):​c.285G>A​(p.Gln95Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000078 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IQSEC3 NM_001170738.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.72
• Publications: 0 publications found

Genes affected

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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 12-67167-G-A is Benign according to our data. Variant chr12-67167-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2642555.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.72 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IQSEC3	NM_001170738.2	c.285G>A	p.Gln95Gln	synonymous_variant	Exon 1 of 14	ENST00000538872.6	NP_001164209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IQSEC3	ENST00000538872.6	c.285G>A	p.Gln95Gln	synonymous_variant	Exon 1 of 14	5	NM_001170738.2	ENSP00000437554.1

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152232 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000135 AC: 17 AN: 126134 AF XY: 0.000203

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000842

Gnomad ASJ exome AF: 0.00132

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000627

Gnomad OTH exome AF: 0.000255

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000776 AC: 107 AN: 1379264 Hom.: 0 Cov.: 36 AF XY: 0.0000882 AC XY: 60 AN XY: 680378

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000478 AC: 15 AN: 31370

American (AMR) AF: 0.0000562 AC: 2 AN: 35612

Ashkenazi Jewish (ASJ) AF: 0.00148 AC: 37 AN: 24996

East Asian (EAS) AF: 0.00 AC: 0 AN: 35700

South Asian (SAS) AF: 0.000114 AC: 9 AN: 78980

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33872

Middle Eastern (MID) AF: 0.000490 AC: 2 AN: 4082

European-Non Finnish (NFE) AF: 0.0000279 AC: 30 AN: 1077084

Other (OTH) AF: 0.000208 AC: 12 AN: 57568

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000919 AC: 14 AN: 152346 Hom.: 0 Cov.: 34 AF XY: 0.0000805 AC XY: 6 AN XY: 74496

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000217 AC: 9 AN: 41560

American (AMR) AF: 0.0000653 AC: 1 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2114

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.004292), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000192 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

IQSEC3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	11
DANN	Benign	0.97
PhyloP100		1.7
PromoterAI		0.079	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs563815894; hg19: chr12-176333;