3-197943835-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_032263.5(IQCG):c.225C>G(p.Leu75=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00501 in 1,614,112 control chromosomes in the GnomAD database, including 363 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.026 (217 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (146 hom.)
• Consequence: IQCG NM_032263.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.392

Genes affected

IQCG (HGNC:25251): (IQ motif containing G) Enables Hsp70 protein binding activity and calmodulin binding activity. Predicted to be involved in sperm axoneme assembly. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 3-197943835-G-C is Benign according to our data. Variant chr3-197943835-G-C is described in ClinVar as [Benign]. Clinvar id is 783413.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.392 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IQCG	NM_032263.5	c.225C>G	p.Leu75=	synonymous_variant	4/12	ENST00000265239.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQCG	ENST00000265239.11	c.225C>G	p.Leu75=	synonymous_variant	4/12	1	NM_032263.5	P1

Frequencies

GnomAD3 genomes AF: 0.0264 AC: 4014 AN: 152150 Hom.: 216 Cov.: 32

Gnomad AFR AF: 0.0929

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00754

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.0129

GnomAD3 exomes AF: 0.00684 AC: 1720 AN: 251476 Hom.: 86 AF XY: 0.00498 AC XY: 677 AN XY: 135906

Gnomad AFR exome AF: 0.0930

Gnomad AMR exome AF: 0.00390

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000440

Gnomad OTH exome AF: 0.00293

GnomAD4 exome AF: 0.00278 AC: 4070 AN: 1461844 Hom.: 146 Cov.: 32 AF XY: 0.00239 AC XY: 1735 AN XY: 727226

Gnomad4 AFR exome AF: 0.0962

Gnomad4 AMR exome AF: 0.00470

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000227

Gnomad4 OTH exome AF: 0.00571

GnomAD4 genome AF: 0.0264 AC: 4024 AN: 152268 Hom.: 217 Cov.: 32 AF XY: 0.0254 AC XY: 1891 AN XY: 74450

Gnomad4 AFR AF: 0.0929

Gnomad4 AMR AF: 0.00753

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000323

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00819 Hom.: 9

Bravo AF: 0.0304

Asia WGS AF: 0.00635 AC: 22 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000830

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 18, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	1.9
Dann	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs34070639; hg19: chr3-197670706;