3-197938620-T-G

Variant names:

• chr3-197938620-T-G
• NM_032263.5:c.443A>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032263.5(IQCG):​c.443A>C​(p.Asp148Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: IQCG NM_032263.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.88

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3564682).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IQCG	NM_032263.5	c.443A>C	p.Asp148Ala	missense_variant	Exon 5 of 12	ENST00000265239.11	NP_115639.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IQCG	ENST00000265239.11	c.443A>C	p.Asp148Ala	missense_variant	Exon 5 of 12	1	NM_032263.5	ENSP00000265239.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461892 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.022	T;T;.;.
Eigen	Benign	0.12
Eigen_PC	Benign	0.086
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.69	.;T;T;T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.36	T;T;T;T
MetaSVM	Benign	-0.76	T
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.9	D;D;D;D
REVEL	Benign	0.23
Sift	Uncertain	0.011	D;D;D;D
Sift4G	Uncertain	0.016	D;D;D;.
Polyphen		0.73	P;P;D;.
Vest4		0.51
MutPred		0.50		Gain of MoRF binding (P = 0.0373);Gain of MoRF binding (P = 0.0373);Gain of MoRF binding (P = 0.0373);.;
MVP		0.67
MPC		0.56
ClinPred		0.85	D
GERP RS		5.5
Varity_R		0.27
gMVP		0.27

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: chr3-197665491;