Variant 22-25028244-C-T 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.245C>T(p.Pro82Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000307 in 1,551,674 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00032 ( 0 hom. )

Consequence

KIAA1671
NM_001145206.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0530

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=0.0270136).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA1671	NM_001145206.2 linkuse as main transcript	c.245C>T	p.Pro82Leu	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.245C>T	p.Pro82Leu	missense_variant	3/13	1	NM_001145206.2	ENSP00000351207.3		Q9BY89-1
KIAA1671	ENST00000406486.8 linkuse as main transcript	c.245C>T	p.Pro82Leu	missense_variant	4/14	5		ENSP00000385152.3		Q9BY89-1

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000964

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.000324

AC:

453

AN:

1399320

Hom.:

Cov.:

AF XY:

0.000317

AC XY:

219

AN XY:

690184

show subpopulations

Gnomad4 AFR exome

AF:

0.0000316

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00218

Gnomad4 EAS exome

AF:

0.0000560

Gnomad4 SAS exome

AF:

0.000429

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000313

Gnomad4 OTH exome

AF:

0.000241

GnomAD4 genome

AF:

0.000151

AC:

AN:

152354

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.000473

Bravo

AF:

0.000249

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

Jul 28, 2021

The c.245C>T (p.P82L) alteration is located in exon 1 (coding exon 1) of the KIAA1671 gene. This alteration results from a C to T substitution at nucleotide position 245, causing the proline (P) at amino acid position 82 to be replaced by a leucine (L). 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

0.082

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

1.2

DANN

Benign

0.95

DEOGEN2

Benign

0.0097

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.088

LIST_S2

Benign

0.40

.;T

M_CAP

Benign

0.073

MetaRNN

Benign

0.027

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.60

N;N

REVEL

Benign

0.0060

Sift

Uncertain

0.022

D;D

Sift4G

Benign

0.12

T;T

Polyphen

0.017

B;B

Vest4

0.059

MutPred

0.26

Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);

MVP

0.067

ClinPred

0.032

GERP RS

-1.7

Varity_R

0.025

gMVP

0.094

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