Variant chr3-51896889-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152397.3(IQCF1):c.114A>C(p.Lys38Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. K38T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

IQCF1
NM_152397.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.24

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]

IQCF1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04937339).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
IQCF1	NM_152397.3 linkuse as main transcript	c.114A>C	p.Lys38Asn	missense_variant	3/4	ENST00000310914.10
IQCF1	XM_011533366.2 linkuse as main transcript	c.9A>C	p.Lys3Asn	missense_variant	2/3
IQCF1	XM_017005729.1 linkuse as main transcript	c.9A>C	p.Lys3Asn	missense_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQCF1	ENST00000310914.10 linkuse as main transcript	c.114A>C	p.Lys38Asn	missense_variant	3/4	1	NM_152397.3	P1	Q8N6M8-1
IQCF1	ENST00000314534.6 linkuse as main transcript	c.*35A>C		3_prime_UTR_variant, NMD_transcript_variant	4/5	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460600

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726718

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 submitter

clinical testing

Ambry Genetics

Jul 30, 2023

The c.114A>C (p.K38N) alteration is located in exon 3 (coding exon 3) of the IQCF1 gene. This alteration results from a A to C substitution at nucleotide position 114, causing the lysine (K) at amino acid position 38 to be replaced by an asparagine (N). 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

0.12

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.70

DANN

Benign

0.20

DEOGEN2

Benign

0.0014

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.28

M_CAP

Benign

0.0025

MetaRNN

Benign

0.049

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.20

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.25

REVEL

Benign

0.036

Sift

Benign

0.23

Sift4G

Benign

0.29

Polyphen

0.0010

Vest4

0.074

MutPred

0.21

Loss of ubiquitination at K38 (P = 0.0041);

MVP

0.030

MPC

0.075

ClinPred

0.18

GERP RS

-6.3

Varity_R

0.044

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over