rs374725274

Variant names:

• chr15-67357415-A-C
• rs374725274
• NM_001031715.3:c.708A>C

Your query was ambiguous. Multiple possible variants found:

• chr15-67357415-A-C
• chr15-67357415-A-G
• chr15-67357415-A-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.708A>C​(p.Arg236Ser) 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. 16/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IQCH NM_001031715.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.222
• Publications: 0 publications found

Genes affected

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

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

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=0.028639823).

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.708A>C	p.Arg236Ser	missense	Exon 7 of 21	NP_001026885.2	Q86VS3-1
	IQCH	NM_001322475.2		c.189A>C	p.Arg63Ser	missense	Exon 5 of 18	NP_001309404.2
	IQCH	NM_001322470.2		c.189A>C	p.Arg63Ser	missense	Exon 4 of 16	NP_001309399.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQCH	ENST00000335894.9	TSL:1 MANE Select	c.708A>C	p.Arg236Ser	missense	Exon 7 of 21	ENSP00000336861.4	Q86VS3-1
	IQCH	ENST00000629425.2	TSL:1	c.189A>C	p.Arg63Ser	missense	Exon 4 of 7	ENSP00000486970.1	Q86VS3-3
	IQCH	ENST00000514049.5	TSL:2	n.*191A>C		non_coding_transcript_exon	Exon 4 of 17	ENSP00000421223.1	D6RGG0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.31
DANN	Benign	0.20
DEOGEN2	Benign	0.0067	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.22
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.89	N
REVEL	Benign	0.017
Sift	Benign	0.77	T
Sift4G	Benign	0.77	T
Polyphen		0.0	B
Vest4		0.083
MutPred		0.21		Gain of phosphorylation at R236 (P = 0.007)
MVP		0.014
MPC		0.11
ClinPred		0.043	T
GERP RS		-1.8
Varity_R		0.073
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs374725274; hg19: chr15-67649753;