Genetic Variant NM_001031715.3:c.773C>T (chr15-67372130-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.773C>T(p.Pro258Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,455,400 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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: 0.0000014 ( 0 hom. )

Consequence

IQCH
NM_001031715.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.380

Publications

0 publications found

Variant links:

Genes affected

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

IQCH links:

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

IQCH-AS1 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=0.09036228).

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.773C>T	p.Pro258Leu	missense	Exon 9 of 21	NP_001026885.2	Q86VS3-1
IQCH	NM_001322475.2		c.254C>T	p.Pro85Leu	missense	Exon 7 of 18	NP_001309404.2
IQCH	NM_001322470.2		c.254C>T	p.Pro85Leu	missense	Exon 6 of 16	NP_001309399.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IQCH	ENST00000335894.9	TSL:1 MANE Select	c.773C>T	p.Pro258Leu	missense	Exon 9 of 21	ENSP00000336861.4	Q86VS3-1
IQCH	ENST00000629425.2	TSL:1	c.254C>T	p.Pro85Leu	missense	Exon 6 of 7	ENSP00000486970.1	Q86VS3-3
IQCH	ENST00000514049.5	TSL:2	n.*362C>T		non_coding_transcript_exon	Exon 7 of 17	ENSP00000421223.1	D6RGG0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000407

AC:

AN:

245806

AF XY:

0.00000752

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000550

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1455400

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

723486

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32998

American (AMR)

AF:

0.00

AC:

AN:

43548

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25854

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39630

South Asian (SAS)

AF:

0.00

AC:

AN:

84758

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53262

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5712

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109556

Other (OTH)

AF:

0.0000166

AC:

AN:

60082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

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

-0.29

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.24

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.84

M_CAP

Benign

0.020

MetaRNN

Benign

0.090

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.6

PhyloP100

0.38

PrimateAI

Benign

0.24

PROVEAN

Benign

-2.3

REVEL

Benign

0.099

Sift

Benign

0.15

Sift4G

Uncertain

0.0060

Polyphen

0.90

Vest4

0.19

MutPred

0.33

Loss of loop (P = 0.0112)

MVP

0.061

MPC

0.20

ClinPred

0.27

GERP RS

3.5

PromoterAI

-0.0096

Neutral

(source)

Varity_R

0.039

gMVP

0.58

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over