chr3-197938696-T-C

Position:

• chr3-197938696-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032263.5(IQCG):​c.367A>G​(p.Ile123Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: IQCG NM_032263.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.69

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 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=0.04212886).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IQCG	NM_032263.5	c.367A>G	p.Ile123Val	missense_variant	5/12	ENST00000265239.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQCG	ENST00000265239.11	c.367A>G	p.Ile123Val	missense_variant	5/12	1	NM_032263.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Jul 19, 2023

The c.367A>G (p.I123V) alteration is located in exon 5 (coding exon 3) of the IQCG gene. This alteration results from a A to G substitution at nucleotide position 367, causing the isoleucine (I) at amino acid position 123 to be replaced by a valine (V). 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	0.067
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.0030
DANN	Benign	0.24
DEOGEN2	Benign	0.0018	T;T;.;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0081	N
LIST_S2	Benign	0.31	.;T;T;T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.042	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.17	N;N;N;N
REVEL	Benign	0.061
Sift	Benign	0.93	T;T;T;T
Sift4G	Benign	1.0	T;T;T;.
Polyphen		0.0010	B;B;B;.
Vest4		0.044
MutPred		0.091		Gain of glycosylation at T124 (P = 0.0351);Gain of glycosylation at T124 (P = 0.0351);Gain of glycosylation at T124 (P = 0.0351);.;
MVP		0.048
MPC		0.19
ClinPred		0.045	T
GERP RS		-9.9
Varity_R		0.034
gMVP		0.083

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: chr3-197665567;