3-51830542-C-A

Variant names:

• chr3-51830542-C-A
• rs201908745
• NM_001393887.1:c.206C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001393887.1(IQCF3):​c.206C>A​(p.Thr69Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T69M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: IQCF3 NM_001393887.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.356
• Publications: 0 publications found

Genes affected

IQCF3 (HGNC:31816): (IQ motif containing F3) Predicted to enable calmodulin binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000285749 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04412031).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393887.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQCF3	NM_001393887.1	MANE Select	c.206C>A	p.Thr69Lys	missense	Exon 3 of 3	NP_001380816.1	P0C7M6
	IQCF3	NM_001085479.3		c.206C>A	p.Thr69Lys	missense	Exon 7 of 7	NP_001078948.1	P0C7M6
	IQCF3	NM_001207023.2		c.206C>A	p.Thr69Lys	missense	Exon 7 of 7	NP_001193952.1	P0C7M6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQCF3	ENST00000440739.4	TSL:2 MANE Select	c.206C>A	p.Thr69Lys	missense	Exon 3 of 3	ENSP00000402012.2	P0C7M6
	IQCF3	ENST00000437810.7	TSL:1	c.206C>A	p.Thr69Lys	missense	Exon 7 of 7	ENSP00000409373.2	P0C7M6
	IQCF3	ENST00000446775.5	TSL:1	c.206C>A	p.Thr69Lys	missense	Exon 7 of 7	ENSP00000401767.1	P0C7M6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461676 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727122

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111850

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Benign	0.67
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.030	N
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.36
PROVEAN	Benign	2.0	N
REVEL	Benign	0.034
Sift4G	Pathogenic	0.0	D
Vest4		0.10
MutPred		0.21		Gain of sheet (P = 0.0477)
MVP		0.32
ClinPred		0.11	T
GERP RS		-1.5
Varity_R		0.045
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs201908745; hg19: chr3-51864558;