Variant X-119087166-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001394962.1(KIAA1210):c.3536C>T(p.Pro1179Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000203 in 1,210,087 control chromosomes in the GnomAD database, including 1 homozygotes. There are 77 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000080 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.00022 ( 1 hom. 75 hem. )

Consequence

KIAA1210
NM_001394962.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.61

Variant links:

Genes affected

KIAA1210 (HGNC:29218): (KIAA1210) Predicted to be located in acrosomal vesicle. Predicted to colocalize with basal ectoplasmic specialization. [provided by Alliance of Genome Resources, Apr 2022]

KIAA1210 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14950076).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA1210	NM_001394962.1 linkuse as main transcript	c.3536C>T	p.Pro1179Leu	missense_variant	9/12	ENST00000691062.1	NP_001381891.1
KIAA1210	NM_020721.1 linkuse as main transcript	c.4064C>T	p.Pro1355Leu	missense_variant	11/14		NP_065772.1	Q9ULL0
KIAA1210	XM_017029688.3 linkuse as main transcript	c.3581C>T	p.Pro1194Leu	missense_variant	9/12		XP_016885177.1
KIAA1210	XM_017029689.3 linkuse as main transcript	c.3383C>T	p.Pro1128Leu	missense_variant	8/11		XP_016885178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA1210	ENST00000691062.1 linkuse as main transcript	c.3536C>T	p.Pro1179Leu	missense_variant	9/12		NM_001394962.1	ENSP00000510348.1		A0A8I5KWH9
KIAA1210	ENST00000402510.2 linkuse as main transcript	c.4064C>T	p.Pro1355Leu	missense_variant	11/14	5		ENSP00000384670.2		Q9ULL0

Frequencies

GnomAD3 genomes

AF:

0.0000803

AC:

AN:

112095

Hom.:

Cov.:

AF XY:

0.0000584

AC XY:

AN XY:

34261

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000169

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000121

AC:

AN:

181505

Hom.:

AF XY:

0.000104

AC XY:

AN XY:

67477

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.000258

Gnomad OTH exome

AF:

0.000224

GnomAD4 exome

AF:

0.000216

AC:

237

AN:

1097992

Hom.:

Cov.:

AF XY:

0.000206

AC XY:

AN XY:

363422

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000264

Gnomad4 OTH exome

AF:

0.000326

GnomAD4 genome

AF:

0.0000803

AC:

AN:

112095

Hom.:

Cov.:

AF XY:

0.0000584

AC XY:

AN XY:

34261

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.000169

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000347

Hom.:

Bravo

AF:

0.000102

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000692

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000154

AC:

ExAC

AF:

0.0000662

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000474

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 06, 2024

The c.4064C>T (p.P1355L) alteration is located in exon 11 (coding exon 11) of the KIAA1210 gene. This alteration results from a C to T substitution at nucleotide position 4064, causing the proline (P) at amino acid position 1355 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

0.14

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.048

FATHMM_MKL

Benign

0.068

LIST_S2

Benign

0.57

M_CAP

Benign

0.0088

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PrimateAI

Benign

0.28

PROVEAN

Pathogenic

-5.0

REVEL

Benign

0.041

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.0080

Polyphen

0.96

Vest4

0.17

MVP

0.085

MPC

0.24

ClinPred

0.29

GERP RS

0.16

Varity_R

0.073

gMVP

0.088

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