Variant chr19-18257307-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001145304.2(IQCN):c.3977C>T(p.Ala1326Val) variant causes a missense change. The variant allele was found at a frequency of 0.000013 in 1,613,372 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

IQCN
NM_001145304.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.81

Variant links:

Genes affected

IQCN (HGNC:29350): (IQ motif containing N) Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

IQCN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
IQCN	NM_001145304.2 linkuse as main transcript	c.3977C>T	p.Ala1326Val	missense_variant	4/4	ENST00000392413.5
IQCN	NM_025249.4 linkuse as main transcript	c.3416C>T	p.Ala1139Val	missense_variant	4/4
IQCN	NM_001145305.2 linkuse as main transcript	c.3278C>T	p.Ala1093Val	missense_variant	4/4
IQCN	XM_005260084.2 linkuse as main transcript	c.3977C>T	p.Ala1326Val	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQCN	ENST00000392413.5 linkuse as main transcript	c.3977C>T	p.Ala1326Val	missense_variant	4/4	1	NM_001145304.2	A2	Q9H0B3-4
IQCN	ENST00000600328.7 linkuse as main transcript	c.3416C>T	p.Ala1139Val	missense_variant	4/4	1		P2	Q9H0B3-1
IQCN	ENST00000600359.7 linkuse as main transcript	c.3278C>T	p.Ala1093Val	missense_variant	4/4	2		A2	Q9H0B3-5
IQCN	ENST00000599638.2 linkuse as main transcript	n.5312C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250430

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135582

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461114

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

726896

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000579

Hom.:

Bravo

AF:

0.0000982

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 31, 2022

The c.3977C>T (p.A1326V) alteration is located in exon 4 (coding exon 3) of the KIAA1683 gene. This alteration results from a C to T substitution at nucleotide position 3977, causing the alanine (A) at amino acid position 1326 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

-0.057

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

T;T;.;.

Eigen

Uncertain

0.39

Eigen_PC

Benign

0.22

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.82

T;T;T;T

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.68

D;D;D;D

MetaSVM

Uncertain

-0.10

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.44

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

.;D;.;.

Vest4

0.63

MVP

0.66

MPC

0.73

ClinPred

0.93

GERP RS

4.7

Varity_R

0.40

gMVP

0.21

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over