3-197926073-A-G

Position:

• chr3-197926073-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_032263.5(IQCG):​c.677T>C​(p.Leu226Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IQCG NM_032263.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.54

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]

IQCG (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.917

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQCG	NM_032263.5	c.677T>C	p.Leu226Pro	missense_variant	7/12	ENST00000265239.11	NP_115639.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IQCG	ENST00000265239.11	c.677T>C	p.Leu226Pro	missense_variant	7/12	1	NM_032263.5	ENSP00000265239.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1433342 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 714862

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

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

Aug 26, 2024

The c.677T>C (p.L226P) alteration is located in exon 7 (coding exon 5) of the IQCG gene. This alteration results from a T to C substitution at nucleotide position 677, causing the leucine (L) at amino acid position 226 to be replaced by a proline (P). 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	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.33
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.46	T;T;.
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.71	.;T;T
M_CAP	Pathogenic	0.37	D
MetaRNN	Pathogenic	0.92	D;D;D
MetaSVM	Uncertain	0.47	D
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-6.0	D;D;D
REVEL	Pathogenic	0.84
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.0080	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.84
MutPred		0.72		Gain of disorder (P = 0.0224);Gain of disorder (P = 0.0224);Gain of disorder (P = 0.0224);
MVP		0.94
MPC		1.1
ClinPred		1.0	D
GERP RS		4.4
Varity_R		0.95
gMVP		0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr3-197652944;