Genetic Variant NM_001393887.1:c.206C>T (chr3-51830542-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001393887.1(IQCF3):c.206C>T(p.Thr69Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000756 in 1,613,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000057 ( 0 hom. )

Consequence

IQCF3
NM_001393887.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.356

Publications

0 publications found

Variant links:

Genes affected

IQCF3 (HGNC:31816): (IQ motif containing F3) Predicted to enable calmodulin binding activity. [provided by Alliance of Genome Resources, Apr 2022]

IQCF3 links:

ENSG00000285749 (HGNC:):

ENSG00000285749 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.045152813).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393887.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IQCF3	NM_001393887.1	MANE Select	c.206C>T	p.Thr69Met	missense	Exon 3 of 3	NP_001380816.1	P0C7M6
IQCF3	NM_001085479.3		c.206C>T	p.Thr69Met	missense	Exon 7 of 7	NP_001078948.1	P0C7M6
IQCF3	NM_001207023.2		c.206C>T	p.Thr69Met	missense	Exon 7 of 7	NP_001193952.1	P0C7M6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IQCF3	ENST00000440739.4	TSL:2 MANE Select	c.206C>T	p.Thr69Met	missense	Exon 3 of 3	ENSP00000402012.2	P0C7M6
IQCF3	ENST00000437810.7	TSL:1	c.206C>T	p.Thr69Met	missense	Exon 7 of 7	ENSP00000409373.2	P0C7M6
IQCF3	ENST00000446775.5	TSL:1	c.206C>T	p.Thr69Met	missense	Exon 7 of 7	ENSP00000401767.1	P0C7M6

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000821

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000922

AC:

AN:

249344

AF XY:

0.0000888

show subpopulations

Gnomad AFR exome

AF:

0.000642

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000568

AC:

AN:

1461676

Hom.:

Cov.:

AF XY:

0.0000564

AC XY:

AN XY:

727122

show subpopulations

African (AFR)

AF:

0.000896

AC:

AN:

33480

American (AMR)

AF:

0.0000671

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.000290

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000540

AC:

AN:

1111850

Other (OTH)

AF:

0.000282

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000256

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.000821

AC:

AN:

41432

American (AMR)

AF:

0.0000654

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.000829

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000136

Hom.:

Bravo

AF:

0.000359

ESP6500AA

AF:

0.000909

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000140

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.018

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.78

M_CAP

Benign

0.012

MetaRNN

Benign

0.045

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.86

PhyloP100

-0.36

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.73

REVEL

Benign

0.022

Sift

Benign

0.16

Sift4G

Benign

0.14

Polyphen

0.58

Vest4

0.081

MVP

0.12

MPC

0.19

ClinPred

0.012

GERP RS

-1.5

Varity_R

0.019

gMVP

0.075

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over