Variant X-119086713-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_001394962.1(KIAA1210):c.3989G>A(p.Gly1330Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000163 in 1,209,467 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 56 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00087 ( 0 hom., 28 hem., cov: 23)

Exomes 𝑓: 0.000091 ( 0 hom. 28 hem. )

Consequence

KIAA1210
NM_001394962.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.873

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014457434).

BS2

High Hemizygotes in GnomAd4 at 28 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA1210	NM_001394962.1 linkuse as main transcript	c.3989G>A	p.Gly1330Asp	missense_variant	9/12	ENST00000691062.1	NP_001381891.1
KIAA1210	NM_020721.1 linkuse as main transcript	c.4517G>A	p.Gly1506Asp	missense_variant	11/14		NP_065772.1	Q9ULL0
KIAA1210	XM_017029688.3 linkuse as main transcript	c.4034G>A	p.Gly1345Asp	missense_variant	9/12		XP_016885177.1
KIAA1210	XM_017029689.3 linkuse as main transcript	c.3836G>A	p.Gly1279Asp	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.3989G>A	p.Gly1330Asp	missense_variant	9/12		NM_001394962.1	ENSP00000510348.1		A0A8I5KWH9
KIAA1210	ENST00000402510.2 linkuse as main transcript	c.4517G>A	p.Gly1506Asp	missense_variant	11/14	5		ENSP00000384670.2		Q9ULL0

Frequencies

GnomAD3 genomes

AF:

0.000860

AC:

AN:

111595

Hom.:

Cov.:

AF XY:

0.000800

AC XY:

AN XY:

33771

show subpopulations

Gnomad AFR

AF:

0.00306

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000949

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:

0.00

Gnomad OTH

AF:

0.000670

GnomAD3 exomes

AF:

0.000205

AC:

AN:

180593

Hom.:

AF XY:

0.0000900

AC XY:

AN XY:

66633

show subpopulations

Gnomad AFR exome

AF:

0.00227

Gnomad AMR exome

AF:

0.000330

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000911

AC:

100

AN:

1097819

Hom.:

Cov.:

AF XY:

0.0000771

AC XY:

AN XY:

363263

show subpopulations

Gnomad4 AFR exome

AF:

0.00299

Gnomad4 AMR exome

AF:

0.000341

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:

0.00

Gnomad4 OTH exome

AF:

0.000195

GnomAD4 genome

AF:

0.000869

AC:

AN:

111648

Hom.:

Cov.:

AF XY:

0.000828

AC XY:

AN XY:

33834

show subpopulations

Gnomad4 AFR

AF:

0.00309

Gnomad4 AMR

AF:

0.0000948

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000661

Alfa

AF:

0.0000445

Hom.:

Bravo

AF:

0.00111

ESP6500AA

AF:

0.00218

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000215

AC:

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, 2022

The c.4517G>A (p.G1506D) alteration is located in exon 11 (coding exon 11) of the KIAA1210 gene. This alteration results from a G to A substitution at nucleotide position 4517, causing the glycine (G) at amino acid position 1506 to be replaced by an aspartic acid (D). 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

0.22

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.8

DANN

Uncertain

0.99

DEOGEN2

Benign

0.011

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.44

M_CAP

Benign

0.0062

MetaRNN

Benign

0.014

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.9

REVEL

Benign

0.041

Sift

Uncertain

0.014

Sift4G

Uncertain

0.029

Polyphen

0.85

Vest4

0.19

MVP

0.067

MPC

0.27

ClinPred

0.045

GERP RS

-0.35

Varity_R

0.12

gMVP

0.068

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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