3-51895099-T-G

Variant summary

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

The NM_152397.3(IQCF1):ā€‹c.409A>Cā€‹(p.Met137Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000911 in 1,614,106 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 Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00020 ( 0 hom., cov: 32)
Exomes š‘“: 0.000080 ( 0 hom. )

Consequence

IQCF1
NM_152397.3 missense

Scores

3
7
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.64
Variant links:
Genes affected
IQCF1 (HGNC:28607): (IQ motif containing F1) Predicted to enable calmodulin binding activity. Predicted to be involved in positive regulation of acrosome reaction and positive regulation of flagellated sperm motility involved in capacitation. Located in acrosomal vesicle. [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=0.13398072).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IQCF1NM_152397.3 linkuse as main transcriptc.409A>C p.Met137Leu missense_variant 4/4 ENST00000310914.10
IQCF1XM_011533366.2 linkuse as main transcriptc.304A>C p.Met102Leu missense_variant 3/3
IQCF1XM_017005729.1 linkuse as main transcriptc.304A>C p.Met102Leu missense_variant 3/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IQCF1ENST00000310914.10 linkuse as main transcriptc.409A>C p.Met137Leu missense_variant 4/41 NM_152397.3 P1Q8N6M8-1
IQCF1ENST00000314534.6 linkuse as main transcriptc.*330A>C 3_prime_UTR_variant, NMD_transcript_variant 5/53

Frequencies

GnomAD3 genomes
AF:
0.000197
AC:
30
AN:
152212
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00547
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000162
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000123
AC:
31
AN:
251364
Hom.:
0
AF XY:
0.000155
AC XY:
21
AN XY:
135896
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00149
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000132
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000800
AC:
117
AN:
1461894
Hom.:
0
Cov.:
31
AF XY:
0.0000853
AC XY:
62
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00157
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000540
Gnomad4 OTH exome
AF:
0.000215
GnomAD4 genome
AF:
0.000197
AC:
30
AN:
152212
Hom.:
0
Cov.:
32
AF XY:
0.000188
AC XY:
14
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00547
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000162
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000213
Hom.:
0
Bravo
AF:
0.000140
ExAC
AF:
0.000148
AC:
18
EpiCase
AF:
0.000218
EpiControl
AF:
0.000237

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 27, 2022The c.409A>C (p.M137L) alteration is located in exon 4 (coding exon 4) of the IQCF1 gene. This alteration results from a A to C substitution at nucleotide position 409, causing the methionine (M) at amino acid position 137 to be replaced by a leucine (L). 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
Uncertain
0.43
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.27
CADD
Uncertain
25
DANN
Uncertain
0.98
DEOGEN2
Benign
0.30
T
Eigen
Uncertain
0.44
Eigen_PC
Uncertain
0.42
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Benign
0.86
D
M_CAP
Benign
0.022
T
MetaRNN
Benign
0.13
T
MetaSVM
Benign
-0.74
T
MutationAssessor
Pathogenic
3.3
M
MutationTaster
Benign
0.55
N
PrimateAI
Uncertain
0.51
T
PROVEAN
Uncertain
-3.0
D
REVEL
Benign
0.21
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.88
P
Vest4
0.47
MutPred
0.75
Loss of glycosylation at S133 (P = 0.2737);
MVP
0.17
MPC
0.36
ClinPred
0.70
D
GERP RS
4.8
Varity_R
0.74
gMVP
0.51

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: rs201302777; hg19: chr3-51929115; API