15-67359857-G-A

Position:

• chr15-67359857-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001031715.3(IQCH):​c.725G>A​(p.Arg242Lys) 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. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IQCH NM_001031715.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.263

Genes affected

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

IQCH-AS1 (HGNC:44104): (IQCH antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 15-67359857-G-A is Benign according to our data. Variant chr15-67359857-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2479024.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IQCH	NM_001031715.3	c.725G>A	p.Arg242Lys	missense_variant	8/21	ENST00000335894.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQCH	ENST00000335894.9	c.725G>A	p.Arg242Lys	missense_variant	8/21	1	NM_001031715.3	A2
IQCH-AS1	ENST00000669759.1	n.121+61478C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 25, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.4
DANN	Benign	0.86
DEOGEN2	Benign	0.0086	T;.
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.55	T;T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.036	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.010	N;.
MutationTaster	Benign	1.0	D;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.28	N;.
REVEL	Benign	0.099
Sift	Benign	0.96	T;.
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.16
MutPred		0.19		Gain of catalytic residue at R242 (P = 0.077);.;
MVP		0.014
MPC		0.10
ClinPred		0.041	T
GERP RS		1.5
Varity_R		0.048
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.27		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.27		Position offset: -10

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: chr15-67652195;