chr15-67279399-C-T

Variant names:

• chr15-67279399-C-T
• rs1966257020
• NM_001031715.3:c.274C>T

Variant summary

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

The NM_001031715.3(IQCH):​c.274C>T​(p.Leu92Phe) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IQCH NM_001031715.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.144
• Publications: 0 publications found

Genes affected

IQCH (HGNC:25721): (IQ motif containing H)

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=0.03523156).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031715.3. 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
	IQCH	NM_001031715.3	MANE Select	c.274C>T	p.Leu92Phe	missense	Exon 4 of 21	NP_001026885.2	Q86VS3-1
	IQCH	NM_022784.3		c.274C>T	p.Leu92Phe	missense	Exon 4 of 6	NP_073621.2	Q86VS3-5
	IQCH	NM_001322475.2		c.-125C>T		5_prime_UTR	Exon 3 of 18	NP_001309404.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQCH	ENST00000335894.9	TSL:1 MANE Select	c.274C>T	p.Leu92Phe	missense	Exon 4 of 21	ENSP00000336861.4	Q86VS3-1
	IQCH	ENST00000629425.2	TSL:1	c.-12+18005C>T		intron	N/A	ENSP00000486970.1	Q86VS3-3
	IQCH	ENST00000512104.5	TSL:2	c.274C>T	p.Leu92Phe	missense	Exon 4 of 6	ENSP00000427323.1	Q86VS3-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1408098 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 703062

African (AFR) AF: 0.00 AC: 0 AN: 32154

American (AMR) AF: 0.00 AC: 0 AN: 42800

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25590

East Asian (EAS) AF: 0.00 AC: 0 AN: 39086

South Asian (SAS) AF: 0.00 AC: 0 AN: 82938

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5664

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1067998

Other (OTH) AF: 0.00 AC: 0 AN: 58542

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.1
DANN	Uncertain	0.98
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.14
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.068
Sift	Benign	0.21	T
Sift4G	Benign	0.30	T
Polyphen		0.0040	B
Vest4		0.16
MutPred		0.29		Loss of stability (P = 0.0682)
MVP		0.18
MPC		0.11
ClinPred		0.054	T
GERP RS		-0.25
Varity_R		0.039
gMVP		0.085

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs1966257020; hg19: chr15-67571737;