Variant 12-67212-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1

The NM_001170738.2(IQSEC3):c.330T>C(p.Asp110Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00769 in 150,130 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0077 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00083 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

IQSEC3
NM_001170738.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.61

Variant links:

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]

IQSEC3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

PM2

Variant has high frequency in the AFR(0.0292868) population. However there is too low homozygotes in high coverage region: (expected more than 2, got 0).

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 12-67212-T-C is Benign according to our data. Variant chr12-67212-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 783652.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.62 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00769 (1155/150130) while in subpopulation AFR AF= 0.0277 (1094/39518). AF 95% confidence interval is 0.0263. There are 0 homozygotes in gnomad4. There are 529 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQSEC3	NM_001170738.2 linkuse as main transcript	c.330T>C	p.Asp110Asp	synonymous_variant	1/14	ENST00000538872.6	NP_001164209.1	Q9UPP2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IQSEC3	ENST00000538872.6 linkuse as main transcript	c.330T>C	p.Asp110Asp	synonymous_variant	1/14	5	NM_001170738.2	ENSP00000437554.1		Q9UPP2-1

Frequencies

GnomAD3 genomes

AF:

0.00769

AC:

1154

AN:

150010

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0277

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00270

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00680

GnomAD3 exomes

AF:

0.00304

AC:

417

AN:

137128

Hom.:

AF XY:

0.00252

AC XY:

189

AN XY:

74934

show subpopulations

Gnomad AFR exome

AF:

0.0512

Gnomad AMR exome

AF:

0.00233

Gnomad ASJ exome

AF:

0.00159

Gnomad EAS exome

AF:

0.0000915

Gnomad SAS exome

AF:

0.0000441

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000128

Gnomad OTH exome

AF:

0.00120

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000826

AC:

1160

AN:

1405072

Hom.:

Cov.:

AF XY:

0.000724

AC XY:

504

AN XY:

696334

show subpopulations

Gnomad4 AFR exome

AF:

0.0309

Gnomad4 AMR exome

AF:

0.00188

Gnomad4 ASJ exome

AF:

0.000631

Gnomad4 EAS exome

AF:

0.0000533

Gnomad4 SAS exome

AF:

0.0000245

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000485

Gnomad4 OTH exome

AF:

0.00123

GnomAD4 genome

AF:

0.00769

AC:

1155

AN:

150130

Hom.:

Cov.:

AF XY:

0.00721

AC XY:

529

AN XY:

73418

show subpopulations

Gnomad4 AFR

AF:

0.0277

Gnomad4 AMR

AF:

0.00270

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00672

Alfa

AF:

0.00657

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 03, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

9.7

DANN

Benign

0.50

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over