Variant X-119081336-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001394962.1(KIAA1210):c.4595C>T(p.Thr1532Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000104 in 1,186,591 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 38 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., 3 hem., cov: 22)

Exomes 𝑓: 0.00010 ( 0 hom. 35 hem. )

Consequence

KIAA1210
NM_001394962.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.42

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016590834).

BP6

Variant X-119081336-G-A is Benign according to our data. Variant chrX-119081336-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2406143.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA1210	NM_001394962.1 linkuse as main transcript	c.4595C>T	p.Thr1532Met	missense_variant	12/12	ENST00000691062.1	NP_001381891.1
KIAA1210	NM_020721.1 linkuse as main transcript	c.5123C>T	p.Thr1708Met	missense_variant	14/14		NP_065772.1	Q9ULL0
KIAA1210	XM_017029688.3 linkuse as main transcript	c.4640C>T	p.Thr1547Met	missense_variant	12/12		XP_016885177.1
KIAA1210	XM_017029689.3 linkuse as main transcript	c.4442C>T	p.Thr1481Met	missense_variant	11/11		XP_016885178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA1210	ENST00000691062.1 linkuse as main transcript	c.4595C>T	p.Thr1532Met	missense_variant	12/12		NM_001394962.1	ENSP00000510348.1		A0A8I5KWH9
KIAA1210	ENST00000402510.2 linkuse as main transcript	c.5123C>T	p.Thr1708Met	missense_variant	14/14	5		ENSP00000384670.2		Q9ULL0

Frequencies

GnomAD3 genomes

AF:

0.000128

AC:

AN:

109379

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

31915

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00107

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:

0.0000570

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000124

AC:

AN:

161646

Hom.:

AF XY:

0.0000191

AC XY:

AN XY:

52310

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000465

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:

0.000109

Gnomad OTH exome

AF:

0.000258

GnomAD4 exome

AF:

0.000101

AC:

109

AN:

1077212

Hom.:

Cov.:

AF XY:

0.000101

AC XY:

AN XY:

347342

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000520

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000198

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000105

Gnomad4 OTH exome

AF:

0.0000886

GnomAD4 genome

AF:

0.000128

AC:

AN:

109379

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

31915

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00107

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000570

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000181

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000312

AC:

ExAC

AF:

0.000108

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 10, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.058

DANN

Benign

0.074

DEOGEN2

Benign

0.0014

FATHMM_MKL

Benign

0.00056

LIST_S2

Benign

0.32

M_CAP

Benign

0.0037

MetaRNN

Benign

0.017

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-1.4

PrimateAI

Benign

0.40

PROVEAN

Benign

1.8

REVEL

Benign

0.037

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.092

MVP

0.030

MPC

0.033

ClinPred

0.017

GERP RS

1.5

Varity_R

0.021

gMVP

0.25

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