Variant 3-197943911-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_032263.5(IQCG):c.149C>T(p.Pro50Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00083 in 1,613,936 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00070 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00084 ( 3 hom. )

Consequence

IQCG
NM_032263.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.37

Variant links:

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]

IQCG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0061198473).

BP6

Variant 3-197943911-G-A is Benign according to our data. Variant chr3-197943911-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2386254.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-197943911-G-A is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IQCG	NM_032263.5 linkuse as main transcript	c.149C>T	p.Pro50Leu	missense_variant	4/12	ENST00000265239.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQCG	ENST00000265239.11 linkuse as main transcript	c.149C>T	p.Pro50Leu	missense_variant	4/12	1	NM_032263.5	P1	Q9H095-1

Frequencies

GnomAD3 genomes

AF:

0.000697

AC:

106

AN:

152050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00110

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000708

AC:

178

AN:

251478

Hom.:

AF XY:

0.000721

AC XY:

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000781

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00180

Gnomad NFE exome

AF:

0.000923

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000844

AC:

1234

AN:

1461886

Hom.:

Cov.:

AF XY:

0.000824

AC XY:

599

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000738

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00167

Gnomad4 NFE exome

AF:

0.000950

Gnomad4 OTH exome

AF:

0.000762

GnomAD4 genome

AF:

0.000697

AC:

106

AN:

152050

Hom.:

Cov.:

AF XY:

0.000566

AC XY:

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00179

Gnomad4 NFE

AF:

0.00110

Gnomad4 OTH

AF:

0.00144

Alfa

AF:

0.000752

Hom.:

Bravo

AF:

0.000601

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.000618

AC:

EpiCase

AF:

0.000818

EpiControl

AF:

0.000771

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 30, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.0030

DANN

Benign

0.26

DEOGEN2

Benign

0.0029

T;T;.;.;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.018

M_CAP

Benign

0.0070

MetaRNN

Benign

0.0061

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.49

N;N;N;N;N

REVEL

Benign

0.023

Sift

Benign

0.34

T;T;T;T;T

Sift4G

Benign

0.72

T;T;T;.;T

Polyphen

0.0

B;B;B;.;.

Vest4

0.038

MVP

0.076

MPC

0.23

ClinPred

0.0072

GERP RS

-0.38

Varity_R

0.017

gMVP

0.081

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

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