Variant chr22-25029333-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001145206.2(KIAA1671):c.1334G>A(p.Arg445Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000128 in 1,547,642 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

KIAA1671
NM_001145206.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.145

Variant links:

Genes affected

KIAA1671 (HGNC:29345): (KIAA1671)

KIAA1671 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.028899908).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA1671	NM_001145206.2 linkuse as main transcript	c.1334G>A	p.Arg445Gln	missense_variant	3/13	ENST00000358431.8	NP_001138678.1	Q9BY89-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA1671	ENST00000358431.8 linkuse as main transcript	c.1334G>A	p.Arg445Gln	missense_variant	3/13	1	NM_001145206.2	ENSP00000351207.3		Q9BY89-1
KIAA1671	ENST00000406486.8 linkuse as main transcript	c.1334G>A	p.Arg445Gln	missense_variant	4/14	5		ENSP00000385152.3		Q9BY89-1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000580

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.000137

AC:

191

AN:

1395334

Hom.:

Cov.:

AF XY:

0.000150

AC XY:

103

AN XY:

687944

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00210

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000107

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000581

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000473

Bravo

AF:

0.0000264

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.1334G>A (p.R445Q) alteration is located in exon 1 (coding exon 1) of the KIAA1671 gene. This alteration results from a G to A substitution at nucleotide position 1334, causing the arginine (R) at amino acid position 445 to be replaced by a glutamine (Q). 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

0.078

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0017

T;T

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.48

.;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.029

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

0.49

N;N

REVEL

Benign

0.028

Sift

Benign

0.47

T;T

Sift4G

Benign

0.51

T;T

Polyphen

0.014

B;B

Vest4

0.057

MutPred

0.27

Loss of MoRF binding (P = 0.0308);Loss of MoRF binding (P = 0.0308);

MVP

0.17

ClinPred

0.050

GERP RS

1.5

Varity_R

0.022

gMVP

0.048

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