X-119087112-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001394962.1(KIAA1210):​c.3590A>T​(p.Gln1197Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000892 in 112,128 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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 0.0000089 ( 0 hom., 0 hem., cov: 22)

Consequence

KIAA1210
NM_001394962.1 missense

Scores

3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.07
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.097625524).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KIAA1210NM_001394962.1 linkuse as main transcriptc.3590A>T p.Gln1197Leu missense_variant 9/12 ENST00000691062.1 NP_001381891.1
KIAA1210NM_020721.1 linkuse as main transcriptc.4118A>T p.Gln1373Leu missense_variant 11/14 NP_065772.1 Q9ULL0
KIAA1210XM_017029688.3 linkuse as main transcriptc.3635A>T p.Gln1212Leu missense_variant 9/12 XP_016885177.1
KIAA1210XM_017029689.3 linkuse as main transcriptc.3437A>T p.Gln1146Leu missense_variant 8/11 XP_016885178.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KIAA1210ENST00000691062.1 linkuse as main transcriptc.3590A>T p.Gln1197Leu missense_variant 9/12 NM_001394962.1 ENSP00000510348.1 A0A8I5KWH9
KIAA1210ENST00000402510.2 linkuse as main transcriptc.4118A>T p.Gln1373Leu missense_variant 11/145 ENSP00000384670.2 Q9ULL0

Frequencies

GnomAD3 genomes
AF:
0.00000892
AC:
1
AN:
112128
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
34284
show subpopulations
Gnomad AFR
AF:
0.0000324
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000551
AC:
1
AN:
181371
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
67363
show subpopulations
Gnomad AFR exome
AF:
0.0000807
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
32
GnomAD4 genome
AF:
0.00000892
AC:
1
AN:
112128
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
34284
show subpopulations
Gnomad4 AFR
AF:
0.0000324
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000302
ESP6500AA
AF:
0.000903
AC:
3
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00000827
AC:
1

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 submitterclinical testingAmbry GeneticsJun 16, 2024The c.4118A>T (p.Q1373L) alteration is located in exon 11 (coding exon 11) of the KIAA1210 gene. This alteration results from a A to T substitution at nucleotide position 4118, causing the glutamine (Q) at amino acid position 1373 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
0.16
BayesDel_addAF
Benign
-0.54
T
BayesDel_noAF
Benign
-0.82
CADD
Benign
9.8
DANN
Uncertain
0.98
DEOGEN2
Benign
0.036
T
FATHMM_MKL
Benign
0.027
N
LIST_S2
Benign
0.29
T
M_CAP
Benign
0.0026
T
MetaRNN
Benign
0.098
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L
PrimateAI
Benign
0.27
T
PROVEAN
Uncertain
-2.5
N
REVEL
Benign
0.026
Sift
Uncertain
0.0070
D
Sift4G
Benign
0.20
T
Polyphen
0.94
P
Vest4
0.23
MVP
0.072
MPC
0.043
ClinPred
0.18
T
GERP RS
-0.011
Varity_R
0.082
gMVP
0.10

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.

Other links and lift over

dbSNP: rs369421952; hg19: chrX-118221075; API