Genetic Variant NM_001394962.1:c.4009G>A (chrX-119086693-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001394962.1(KIAA1210):c.4009G>A(p.Gly1337Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000843 in 1,209,732 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 21 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., 11 hem., cov: 22)

Exomes 𝑓: 0.000049 ( 0 hom. 10 hem. )

Consequence

KIAA1210
NM_001394962.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.232

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 -4 ACMG points.

BS2

High Hemizygotes in GnomAd4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA1210	NM_001394962.1 link	c.4009G>A	p.Gly1337Ser	missense_variant	Exon 9 of 12	ENST00000691062.1	NP_001381891.1
KIAA1210	NM_020721.1 link	c.4537G>A	p.Gly1513Ser	missense_variant	Exon 11 of 14		NP_065772.1	Q9ULL0
KIAA1210	XM_017029688.3 link	c.4054G>A	p.Gly1352Ser	missense_variant	Exon 9 of 12		XP_016885177.1
KIAA1210	XM_017029689.3 link	c.3856G>A	p.Gly1286Ser	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.4009G>A	p.Gly1337Ser	missense_variant	Exon 9 of 12		NM_001394962.1	ENSP00000510348.1		A0A8I5KWH9
KIAA1210	ENST00000402510.2 link	c.4537G>A	p.Gly1513Ser	missense_variant	Exon 11 of 14	5		ENSP00000384670.2		Q9ULL0

Frequencies

GnomAD3 genomes

AF:

0.000430

AC:

AN:

111694

Hom.:

Cov.:

AF XY:

0.000325

AC XY:

AN XY:

33888

show subpopulations

Gnomad AFR

AF:

0.00134

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000570

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:

0.000663

GnomAD3 exomes

AF:

0.000121

AC:

AN:

181123

Hom.:

AF XY:

0.000104

AC XY:

AN XY:

67121

show subpopulations

Gnomad AFR exome

AF:

0.00145

Gnomad AMR exome

AF:

0.000110

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000526

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000492

AC:

AN:

1097988

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

363424

show subpopulations

Gnomad4 AFR exome

AF:

0.00170

Gnomad4 AMR exome

AF:

0.0000568

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000130

GnomAD4 genome

AF:

0.000430

AC:

AN:

111744

Hom.:

Cov.:

AF XY:

0.000324

AC XY:

AN XY:

33948

show subpopulations

Gnomad4 AFR

AF:

0.00133

Gnomad4 AMR

AF:

0.000569

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:

0.000655

Alfa

AF:

0.0000318

Hom.:

Bravo

AF:

0.000502

ESP6500AA

AF:

0.00187

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000190

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 24, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4537G>A (p.G1513S) 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 4537, causing the glycine (G) at amino acid position 1513 to be replaced by a serine (S). 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

-0.83

BayesDel_noAF

Benign

-0.97

CADD

Benign

7.4

DANN

Benign

0.92

DEOGEN2

Benign

0.0024

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.36

M_CAP

Benign

0.010

MetaRNN

Benign

0.0080

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.97

REVEL

Benign

0.031

Sift

Benign

0.20

Sift4G

Benign

0.70

Polyphen

0.38

Vest4

0.058

MVP

0.055

MPC

0.25

ClinPred

0.010

GERP RS

0.83

Varity_R

0.056

gMVP

0.048

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.25

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.25

Position offset: 4

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