chrX-119087355-A-G

Position:

• chrX-119087355-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001394962.1(KIAA1210):​c.3347T>C​(p.Leu1116Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,209,799 control chromosomes in the GnomAD database, including 1 homozygotes. There are 396 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 0.00058 (0 hom., 15 hem., cov: 23)
  • Exomes 𝑓: 0.0011 (1 hom. 381 hem.)
• Consequence: KIAA1210 NM_001394962.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 B:2
• Conservation: PhyloP100: -0.590

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.014473438).
• BS2: High Hemizygotes in GnomAd4 at 15 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA1210	NM_001394962.1	c.3347T>C	p.Leu1116Pro	missense_variant	9/12	ENST00000691062.1	NP_001381891.1
KIAA1210	NM_020721.1	c.3875T>C	p.Leu1292Pro	missense_variant	11/14		NP_065772.1
KIAA1210	XM_017029688.3	c.3392T>C	p.Leu1131Pro	missense_variant	9/12		XP_016885177.1
KIAA1210	XM_017029689.3	c.3194T>C	p.Leu1065Pro	missense_variant	8/11		XP_016885178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA1210	ENST00000691062.1	c.3347T>C	p.Leu1116Pro	missense_variant	9/12		NM_001394962.1	ENSP00000510348.1
KIAA1210	ENST00000402510.2	c.3875T>C	p.Leu1292Pro	missense_variant	11/14	5		ENSP00000384670.2

Frequencies

GnomAD3 genomes AF: 0.000581 AC: 65 AN: 111869 Hom.: 0 Cov.: 23 AF XY: 0.000440 AC XY: 15 AN XY: 34059

Gnomad AFR AF: 0.000228

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: 0.00105

Gnomad OTH AF: 0.000661

GnomAD3 exomes AF: 0.000552 AC: 100 AN: 181276 Hom.: 0 AF XY: 0.000505 AC XY: 34 AN XY: 67298

Gnomad AFR exome AF: 0.000162

Gnomad AMR exome AF: 0.0000366

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: 0.00118

Gnomad OTH exome AF: 0.000225

GnomAD4 exome AF: 0.00113 AC: 1243 AN: 1097930 Hom.: 1 Cov.: 32 AF XY: 0.00105 AC XY: 381 AN XY: 363360

Gnomad4 AFR exome AF: 0.0000379

Gnomad4 AMR exome AF: 0.000114

Gnomad4 ASJ exome AF: 0.000103

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000247

Gnomad4 NFE exome AF: 0.00142

Gnomad4 OTH exome AF: 0.000847

GnomAD4 genome AF: 0.000581 AC: 65 AN: 111869 Hom.: 0 Cov.: 23 AF XY: 0.000440 AC XY: 15 AN XY: 34059

Gnomad4 AFR AF: 0.000228

Gnomad4 AMR AF: 0.0000947

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00105

Gnomad4 OTH AF: 0.000661

Alfa AF: 0.00107 Hom.: 46

Bravo AF: 0.000555

TwinsUK AF: 0.00189 AC: 7

ALSPAC AF: 0.00104 AC: 3

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000785 AC: 5

ExAC AF: 0.000695 AC: 84

EpiCase AF: 0.000927

EpiControl AF: 0.000415

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1 Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1 Benign:1

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Ambry Genetics	Dec 09, 2023	The c.3875T>C (p.L1292P) alteration is located in exon 11 (coding exon 11) of the KIAA1210 gene. This alteration results from a T to C substitution at nucleotide position 3875, causing the leucine (L) at amino acid position 1292 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided Benign:1

Likely benign, no assertion criteria provided

clinical testing

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	3.0
DANN	Benign	0.95
DEOGEN2	Benign	0.018	T
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.014	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.8	L
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.071
Sift	Benign	0.12	T
Sift4G	Benign	0.19	T
Polyphen		0.046	B
Vest4		0.42
MVP		0.014
MPC		0.27
ClinPred		0.0099	T
GERP RS		-5.7
Varity_R		0.057
gMVP		0.43

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

Other links and lift over

dbSNP: rs200015496; hg19: chrX-118221318;