Genetic Variant KIAA1210:p.Lys1240Arg (chrX-119086983-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001394962.1(KIAA1210):c.3719A>G(p.Lys1240Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,209,659 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.0000036 ( 0 hom. 1 hem. )

Consequence

KIAA1210
NM_001394962.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.886

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06371623).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA1210	NM_001394962.1 link	c.3719A>G	p.Lys1240Arg	missense_variant	Exon 9 of 12	ENST00000691062.1	NP_001381891.1
KIAA1210	NM_020721.1 link	c.4247A>G	p.Lys1416Arg	missense_variant	Exon 11 of 14		NP_065772.1	Q9ULL0
KIAA1210	XM_017029688.3 link	c.3764A>G	p.Lys1255Arg	missense_variant	Exon 9 of 12		XP_016885177.1
KIAA1210	XM_017029689.3 link	c.3566A>G	p.Lys1189Arg	missense_variant	Exon 8 of 11		XP_016885178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA1210	ENST00000691062.1 link	c.3719A>G	p.Lys1240Arg	missense_variant	Exon 9 of 12		NM_001394962.1	ENSP00000510348.1		A0A8I5KWH9
KIAA1210	ENST00000402510.2 link	c.4247A>G	p.Lys1416Arg	missense_variant	Exon 11 of 14	5		ENSP00000384670.2		Q9ULL0

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111564

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33720

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000191

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:

0.00

GnomAD3 exomes

AF:

0.0000165

AC:

AN:

181493

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

67463

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000110

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:

0.00000364

AC:

AN:

1098095

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363523

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000114

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:

0.00

GnomAD4 genome

AF:

0.0000179

AC:

AN:

111564

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33720

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000191

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:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 18, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4247A>G (p.K1416R) alteration is located in exon 11 (coding exon 11) of the KIAA1210 gene. This alteration results from a A to G substitution at nucleotide position 4247, causing the lysine (K) at amino acid position 1416 to be replaced by an arginine (R). 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

0.10

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-1.0

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0021

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.40

M_CAP

Benign

0.0051

MetaRNN

Benign

0.064

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.90

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.96

REVEL

Benign

0.034

Sift

Benign

0.15

Sift4G

Uncertain

0.056

Polyphen

0.11

Vest4

0.062

MutPred

0.23

Loss of methylation at K1416 (P = 0.012);

MVP

0.040

MPC

0.070

ClinPred

0.046

GERP RS

3.9

Varity_R

0.077

gMVP

0.020

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