chr3-197891545-T-C

Position:

• chr3-197891545-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032263.5(IQCG):​c.1098A>G​(p.Ile366Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000429 in 1,397,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: IQCG NM_032263.5 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.676

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]

ACMG classification

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=0.19466805).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IQCG	NM_032263.5	c.1098A>G	p.Ile366Met	missense_variant, splice_region_variant	11/12	ENST00000265239.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQCG	ENST00000265239.11	c.1098A>G	p.Ile366Met	missense_variant, splice_region_variant	11/12	1	NM_032263.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000429 AC: 6 AN: 1397856 Hom.: 0 Cov.: 23 AF XY: 0.00000572 AC XY: 4 AN XY: 699608

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000569

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 23, 2024

The c.1098A>G (p.I366M) alteration is located in exon 11 (coding exon 9) of the IQCG gene. This alteration results from a A to G substitution at nucleotide position 1098, causing the isoleucine (I) at amino acid position 366 to be replaced by a methionine (M). 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	0.14
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.011	T;T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.69	.;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.94	N;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.95	N;N
REVEL	Benign	0.036
Sift	Benign	0.11	T;T
Sift4G	Benign	0.17	T;T
Polyphen		0.82	P;P
Vest4		0.40
MutPred		0.32		Gain of disorder (P = 0.0455);Gain of disorder (P = 0.0455);
MVP		0.52
MPC		0.53
ClinPred		0.43	T
GERP RS		3.8
Varity_R		0.076
gMVP		0.37

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.

Other links and lift over

hg19: chr3-197618416;