X-119085474-T-G

Position:

• chrX-119085474-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001394962.1(KIAA1210):​c.4229A>C​(p.Gln1410Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 24)
• Consequence: KIAA1210 NM_001394962.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.873

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 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=0.09987661).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA1210	NM_001394962.1	c.4229A>C	p.Gln1410Pro	missense_variant	10/12	ENST00000691062.1	NP_001381891.1
KIAA1210	NM_020721.1	c.4757A>C	p.Gln1586Pro	missense_variant	12/14		NP_065772.1
KIAA1210	XM_017029688.3	c.4274A>C	p.Gln1425Pro	missense_variant	10/12		XP_016885177.1
KIAA1210	XM_017029689.3	c.4076A>C	p.Gln1359Pro	missense_variant	9/11		XP_016885178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA1210	ENST00000691062.1	c.4229A>C	p.Gln1410Pro	missense_variant	10/12		NM_001394962.1	ENSP00000510348.1
KIAA1210	ENST00000402510.2	c.4757A>C	p.Gln1586Pro	missense_variant	12/14	5		ENSP00000384670.2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 16, 2024

The c.4757A>C (p.Q1586P) alteration is located in exon 12 (coding exon 12) of the KIAA1210 gene. This alteration results from a A to C substitution at nucleotide position 4757, causing the glutamine (Q) at amino acid position 1586 to be replaced by a proline (P). 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	0.26
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	13
DANN	Benign	0.97
DEOGEN2	Benign	0.043	T
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.20
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.037	D
Polyphen		0.48	P
Vest4		0.23
MutPred		0.31		Loss of helix (P = 0.0068);
MVP		0.088
MPC		0.037
ClinPred		0.62	D
GERP RS		4.0
Varity_R		0.57
gMVP		0.46

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-118219437;