X-119086998-A-C

Position:

• chrX-119086998-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001394962.1(KIAA1210):​c.3704T>G​(p.Phe1235Cys) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: KIAA1210 NM_001394962.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.541

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048517883).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA1210	NM_001394962.1	c.3704T>G	p.Phe1235Cys	missense_variant	9/12	ENST00000691062.1	NP_001381891.1
KIAA1210	NM_020721.1	c.4232T>G	p.Phe1411Cys	missense_variant	11/14		NP_065772.1
KIAA1210	XM_017029688.3	c.3749T>G	p.Phe1250Cys	missense_variant	9/12		XP_016885177.1
KIAA1210	XM_017029689.3	c.3551T>G	p.Phe1184Cys	missense_variant	8/11		XP_016885178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA1210	ENST00000691062.1	c.3704T>G	p.Phe1235Cys	missense_variant	9/12		NM_001394962.1	ENSP00000510348.1
KIAA1210	ENST00000402510.2	c.4232T>G	p.Phe1411Cys	missense_variant	11/14	5		ENSP00000384670.2

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 22

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

Sep 14, 2023

The c.4232T>G (p.F1411C) alteration is located in exon 11 (coding exon 11) of the KIAA1210 gene. This alteration results from a T to G substitution at nucleotide position 4232, causing the phenylalanine (F) at amino acid position 1411 to be replaced by a cysteine (C). 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	0.25
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.9
DANN	Benign	0.75
DEOGEN2	Benign	0.0040	T
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.014
Sift	Benign	0.17	T
Sift4G	Benign	0.18	T
Polyphen		0.0030	B
Vest4		0.28
MutPred		0.28		Loss of helix (P = 0.0626);
MVP		0.048
MPC		0.25
ClinPred		0.055	T
GERP RS		-10
Varity_R		0.043
gMVP		0.054

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-118220961;