NM_001031715.3:c.481C>T

Variant names:

• chr15-67337068-C-T
• NM_001031715.3:c.481C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001031715.3(IQCH):​c.481C>T​(p.Pro161Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,372 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: IQCH NM_001031715.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.19
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.481C>T	p.Pro161Ser	missense	Exon 5 of 21	NP_001026885.2	Q86VS3-1
	IQCH	NM_001322475.2		c.-11-6995C>T		intron	N/A	NP_001309404.2
	IQCH	NM_001322470.2		c.-11-6995C>T		intron	N/A	NP_001309399.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQCH	ENST00000335894.9	TSL:1 MANE Select	c.481C>T	p.Pro161Ser	missense	Exon 5 of 21	ENSP00000336861.4	Q86VS3-1
	IQCH	ENST00000629425.2	TSL:1	c.-11-6995C>T		intron	N/A	ENSP00000486970.1	Q86VS3-3
	IQCH	ENST00000514049.5	TSL:2	n.175-6995C>T		intron	N/A	ENSP00000421223.1	D6RGG0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461372 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726990

African (AFR) AF: 0.00 AC: 0 AN: 33444

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000720 AC: 8 AN: 1111630

Other (OTH) AF: 0.0000166 AC: 1 AN: 60370

GnomAD4 genome Cov.: 32

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	0.13
BayesDel_addAF	Uncertain	0.041	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.9	L
PhyloP100		4.2
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.23
Sift	Benign	0.14	T
Sift4G	Benign	0.20	T
Polyphen		0.95	P
Vest4		0.66
MutPred		0.53		Loss of glycosylation at T158 (P = 0.0528)
MVP		0.22
MPC		0.52
ClinPred		0.93	D
GERP RS		5.8
Varity_R		0.14
gMVP		0.31
Mutation Taster		=278/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

hg19: chr15-67629406;