Genetic Variant IQCH:p.His19Tyr (chr15-67261275-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001031715.3(IQCH):c.55C>T(p.His19Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000524 in 1,526,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000051 ( 0 hom. )

Consequence

IQCH
NM_001031715.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.04

Publications

0 publications found

Variant links:

Genes affected

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

IQCH links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2165406).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IQCH	NM_001031715.3	MANE Select	c.55C>T	p.His19Tyr	missense	Exon 2 of 21	NP_001026885.2	Q86VS3-1
IQCH	NM_022784.3		c.55C>T	p.His19Tyr	missense	Exon 2 of 6	NP_073621.2	Q86VS3-5
IQCH	NM_001322475.2		c.-249C>T		5_prime_UTR	Exon 2 of 18	NP_001309404.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IQCH	ENST00000335894.9	TSL:1 MANE Select	c.55C>T	p.His19Tyr	missense	Exon 2 of 21	ENSP00000336861.4	Q86VS3-1
IQCH	ENST00000629425.2	TSL:1	c.-131C>T		5_prime_UTR	Exon 2 of 7	ENSP00000486970.1	Q86VS3-3
IQCH	ENST00000512104.5	TSL:2	c.55C>T	p.His19Tyr	missense	Exon 2 of 6	ENSP00000427323.1	Q86VS3-5

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152002

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000143

AC:

AN:

210144

AF XY:

0.00000868

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000953

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000204

GnomAD4 exome

AF:

0.00000509

AC:

AN:

1374842

Hom.:

Cov.:

AF XY:

0.00000291

AC XY:

AN XY:

686492

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29320

American (AMR)

AF:

0.000198

AC:

AN:

30298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24292

East Asian (EAS)

AF:

0.00

AC:

AN:

37740

South Asian (SAS)

AF:

0.00

AC:

AN:

77286

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52800

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5324

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1060886

Other (OTH)

AF:

0.0000176

AC:

AN:

56896

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.432

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152002

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41378

American (AMR)

AF:

0.00

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10570

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68000

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000412

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.048

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.75

M_CAP

Benign

0.020

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.9

PhyloP100

4.0

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.8

REVEL

Benign

0.090

Sift

Uncertain

0.012

Sift4G

Pathogenic

0.0

Polyphen

0.83

Vest4

0.46

MutPred

0.42

Gain of phosphorylation at H19 (P = 0.0728)

MVP

0.30

MPC

0.31

ClinPred

0.76

GERP RS

5.8

Varity_R

0.064

gMVP

0.27

Mutation Taster

=75/25

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over