X-119087094-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001394962.1(KIAA1210):​c.3608C>T​(p.Ser1203Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00021 in 1,209,840 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 87 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., 3 hem., cov: 23)
Exomes 𝑓: 0.00021 ( 0 hom. 84 hem. )

Consequence

KIAA1210
NM_001394962.1 missense

Scores

3
14

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 2.22
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 Benign. Variant got -9 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.045228243).
BP6
Variant X-119087094-G-A is Benign according to our data. Variant chrX-119087094-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2290753.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}. Variant chrX-119087094-G-A is described in Lovd as [Likely_benign].
BS2
High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KIAA1210NM_001394962.1 linkc.3608C>T p.Ser1203Phe missense_variant 9/12 ENST00000691062.1 NP_001381891.1
KIAA1210NM_020721.1 linkc.4136C>T p.Ser1379Phe missense_variant 11/14 NP_065772.1 Q9ULL0
KIAA1210XM_017029688.3 linkc.3653C>T p.Ser1218Phe missense_variant 9/12 XP_016885177.1
KIAA1210XM_017029689.3 linkc.3455C>T p.Ser1152Phe missense_variant 8/11 XP_016885178.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KIAA1210ENST00000691062.1 linkc.3608C>T p.Ser1203Phe missense_variant 9/12 NM_001394962.1 ENSP00000510348.1 A0A8I5KWH9
KIAA1210ENST00000402510.2 linkc.4136C>T p.Ser1379Phe missense_variant 11/145 ENSP00000384670.2 Q9ULL0

Frequencies

GnomAD3 genomes
AF:
0.000214
AC:
24
AN:
111983
Hom.:
0
Cov.:
23
AF XY:
0.0000879
AC XY:
3
AN XY:
34135
show subpopulations
Gnomad AFR
AF:
0.0000325
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000947
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:
0.000414
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000237
AC:
43
AN:
181376
Hom.:
0
AF XY:
0.000252
AC XY:
17
AN XY:
67364
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:
0.000480
Gnomad OTH exome
AF:
0.000224
GnomAD4 exome
AF:
0.000210
AC:
230
AN:
1097803
Hom.:
0
Cov.:
32
AF XY:
0.000231
AC XY:
84
AN XY:
363237
show subpopulations
Gnomad4 AFR exome
AF:
0.0000379
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:
0.0000247
Gnomad4 NFE exome
AF:
0.000261
Gnomad4 OTH exome
AF:
0.0000651
GnomAD4 genome
AF:
0.000214
AC:
24
AN:
112037
Hom.:
0
Cov.:
23
AF XY:
0.0000877
AC XY:
3
AN XY:
34199
show subpopulations
Gnomad4 AFR
AF:
0.0000324
Gnomad4 AMR
AF:
0.0000945
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000414
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000423
Hom.:
16
Bravo
AF:
0.000261
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000310
AC:
2
ExAC
AF:
0.000306
AC:
37
EpiCase
AF:
0.000600
EpiControl
AF:
0.000948

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsNov 17, 2022The c.4136C>T (p.S1379F) alteration is located in exon 11 (coding exon 11) of the KIAA1210 gene. This alteration results from a C to T substitution at nucleotide position 4136, causing the serine (S) at amino acid position 1379 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenNov 01, 2022KIAA1210: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.22
BayesDel_addAF
Benign
-0.59
T
BayesDel_noAF
Benign
-0.75
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.15
T
FATHMM_MKL
Benign
0.17
N
LIST_S2
Benign
0.53
T
M_CAP
Benign
0.0095
T
MetaRNN
Benign
0.045
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
1.4
L
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-2.2
N
REVEL
Benign
0.045
Sift
Uncertain
0.0040
D
Sift4G
Uncertain
0.0070
D
Polyphen
0.10
B
Vest4
0.14
MVP
0.081
MPC
0.24
ClinPred
0.063
T
GERP RS
2.4
Varity_R
0.099
gMVP
0.099

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.

Other links and lift over

dbSNP: rs200034820; hg19: chrX-118221057; COSMIC: COSV99081425; API