Variant 20-38213655-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001029864.2(KIAA1755):c.2990G>A(p.Arg997His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000145 in 1,606,278 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

KIAA1755
NM_001029864.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.53

Variant links:

Genes affected

KIAA1755 (HGNC:29372): (KIAA1755)

KIAA1755 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15854841).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA1755	NM_001029864.2 linkuse as main transcript	c.2990G>A	p.Arg997His	missense_variant	14/14	ENST00000279024.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
KIAA1755	ENST00000279024.9 linkuse as main transcript	c.2990G>A	p.Arg997His	missense_variant	14/14	5	NM_001029864.2	P2
KIAA1755	ENST00000460881.5 linkuse as main transcript	n.1166G>A		non_coding_transcript_exon_variant	3/3	1
KIAA1755	ENST00000487506.1 linkuse as main transcript	n.942G>A		non_coding_transcript_exon_variant	2/2	1
KIAA1755	ENST00000484362.1 linkuse as main transcript	n.1269G>A		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000671

AC:

AN:

238540

Hom.:

AF XY:

0.0000541

AC XY:

AN XY:

129382

show subpopulations

Gnomad AFR exome

AF:

0.0000655

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS exome

AF:

0.0000345

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000111

Gnomad OTH exome

AF:

0.000172

GnomAD4 exome

AF:

0.000151

AC:

220

AN:

1454058

Hom.:

Cov.:

AF XY:

0.000151

AC XY:

109

AN XY:

722698

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000177

Gnomad4 SAS exome

AF:

0.0000705

Gnomad4 FIN exome

AF:

0.0000193

Gnomad4 NFE exome

AF:

0.000181

Gnomad4 OTH exome

AF:

0.0000833

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000828

Hom.:

Bravo

AF:

0.0000907

ExAC

AF:

0.0000659

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

Aug 16, 2021

The c.2990G>A (p.R997H) alteration is located in exon 14 (coding exon 14) of the KIAA1755 gene. This alteration results from a G to A substitution at nucleotide position 2990, causing the arginine (R) at amino acid position 997 to be replaced by a histidine (H). 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

Benign

0.17

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.47

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Benign

0.0065

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.049

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.78

M_CAP

Benign

0.0093

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

MutationTaster

Benign

0.90

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.34

REVEL

Benign

0.10

Sift

Benign

0.19

Sift4G

Benign

0.14

Polyphen

0.53

Vest4

0.39

MVP

0.33

MPC

0.28

ClinPred

0.072

GERP RS

3.2

Varity_R

0.048

gMVP

0.13

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