Variant chr22-25029006-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001145206.2(KIAA1671):c.1007C>T(p.Pro336Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000323 in 1,510,140 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00034 ( 4 hom. )

Consequence

KIAA1671
NM_001145206.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.635

Variant links:

Genes affected

KIAA1671 (HGNC:29345): (KIAA1671)

KIAA1671 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015227675).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA1671	NM_001145206.2 linkuse as main transcript	c.1007C>T	p.Pro336Leu	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.1007C>T	p.Pro336Leu	missense_variant	3/13	1	NM_001145206.2	ENSP00000351207.3		Q9BY89-1
KIAA1671	ENST00000406486.8 linkuse as main transcript	c.1007C>T	p.Pro336Leu	missense_variant	4/14	5		ENSP00000385152.3		Q9BY89-1

Frequencies

GnomAD3 genomes

AF:

0.000184

AC:

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00538

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000339

AC:

460

AN:

1357768

Hom.:

Cov.:

AF XY:

0.000473

AC XY:

315

AN XY:

665926

show subpopulations

Gnomad4 AFR exome

AF:

0.000100

Gnomad4 AMR exome

AF:

0.0000363

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00582

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000189

Gnomad4 OTH exome

AF:

0.000554

GnomAD4 genome

AF:

0.000184

AC:

AN:

152372

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00539

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000416

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

May 27, 2022

The c.1007C>T (p.P336L) 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 1007, causing the proline (P) at amino acid position 336 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

0.12

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

3.7

DANN

Benign

0.51

DEOGEN2

Benign

0.072

T;T

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.53

.;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.015

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;L

PrimateAI

Benign

0.23

PROVEAN

Uncertain

-2.8

D;D

REVEL

Benign

0.029

Sift

Benign

0.18

T;T

Sift4G

Uncertain

0.023

D;D

Polyphen

0.047

B;B

Vest4

0.14

MutPred

0.19

Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);

MVP

0.099

ClinPred

0.11

GERP RS

1.0

Varity_R

0.036

gMVP

0.044

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