chr3-51830556-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001393887.1(IQCF3):​c.220C>T​(p.Arg74Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000688 in 1,613,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R74Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000065 ( 0 hom. )

Consequence

IQCF3
NM_001393887.1 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.442
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10532403).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IQCF3NM_001393887.1 linkc.220C>T p.Arg74Trp missense_variant Exon 3 of 3 ENST00000440739.4 NP_001380816.1
IQCF3NM_001085479.3 linkc.220C>T p.Arg74Trp missense_variant Exon 7 of 7 NP_001078948.1 P0C7M6
IQCF3NM_001207023.2 linkc.220C>T p.Arg74Trp missense_variant Exon 7 of 7 NP_001193952.1 P0C7M6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IQCF3ENST00000440739.4 linkc.220C>T p.Arg74Trp missense_variant Exon 3 of 3 2 NM_001393887.1 ENSP00000402012.2 P0C7M6
ENSG00000285749ENST00000456080.5 linkc.220C>T p.Arg74Trp missense_variant Exon 8 of 8 2 ENSP00000415609.1

Frequencies

GnomAD3 genomes
AF:
0.000105
AC:
16
AN:
152168
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000191
Gnomad OTH
AF:
0.000957
GnomAD3 exomes
AF:
0.0000883
AC:
22
AN:
249252
Hom.:
0
AF XY:
0.0000740
AC XY:
10
AN XY:
135178
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000869
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000159
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.0000650
AC:
95
AN:
1461678
Hom.:
0
Cov.:
31
AF XY:
0.0000619
AC XY:
45
AN XY:
727126
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000894
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000755
Gnomad4 OTH exome
AF:
0.0000663
GnomAD4 genome
AF:
0.000105
AC:
16
AN:
152286
Hom.:
0
Cov.:
32
AF XY:
0.0000806
AC XY:
6
AN XY:
74482
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000191
Gnomad4 OTH
AF:
0.000947
Alfa
AF:
0.0000541
Hom.:
0
Bravo
AF:
0.0000945
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.000148
AC:
18
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 28, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.220C>T (p.R74W) alteration is located in exon 7 (coding exon 3) of the IQCF3 gene. This alteration results from a C to T substitution at nucleotide position 220, causing the arginine (R) at amino acid position 74 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.46
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.044
.;T;T;T
Eigen
Benign
-0.62
Eigen_PC
Benign
-0.78
FATHMM_MKL
Benign
0.037
N
LIST_S2
Benign
0.55
.;.;.;T
M_CAP
Benign
0.0083
T
MetaRNN
Benign
0.11
T;T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.8
.;L;L;L
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-1.5
N;N;N;N
REVEL
Benign
0.059
Sift
Benign
0.035
D;D;D;D
Sift4G
Benign
0.084
T;T;T;T
Polyphen
0.0060
.;B;B;B
Vest4
0.27
MVP
0.31
MPC
0.24
ClinPred
0.071
T
GERP RS
-0.86
Varity_R
0.069
gMVP
0.067

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.

Other links and lift over

dbSNP: rs200102944; hg19: chr3-51864572; COSMIC: COSV101469654; COSMIC: COSV101469654; API