X-119085501-A-G

Position:

• chrX-119085501-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001394962.1(KIAA1210):​c.4202T>C​(p.Val1401Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,392 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: KIAA1210 NM_001394962.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.13

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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03258452).
• BP6: Variant X-119085501-A-G is Benign according to our data. Variant chrX-119085501-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2235541.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA1210	NM_001394962.1	c.4202T>C	p.Val1401Ala	missense_variant	10/12	ENST00000691062.1	NP_001381891.1
KIAA1210	NM_020721.1	c.4730T>C	p.Val1577Ala	missense_variant	12/14		NP_065772.1
KIAA1210	XM_017029688.3	c.4247T>C	p.Val1416Ala	missense_variant	10/12		XP_016885177.1
KIAA1210	XM_017029689.3	c.4049T>C	p.Val1350Ala	missense_variant	9/11		XP_016885178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA1210	ENST00000691062.1	c.4202T>C	p.Val1401Ala	missense_variant	10/12		NM_001394962.1	ENSP00000510348.1
KIAA1210	ENST00000402510.2	c.4730T>C	p.Val1577Ala	missense_variant	12/14	5		ENSP00000384670.2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1097392 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 362840

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000185

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.23
DANN	Benign	0.31
DEOGEN2	Benign	0.00049	T
FATHMM_MKL	Benign	0.0040	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-1.4	N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.40	N
REVEL	Benign	0.022
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.071
MutPred		0.28		Gain of helix (P = 0.0425);
MVP		0.15
MPC		0.036
ClinPred		0.041	T
GERP RS		0.053
Varity_R		0.027
gMVP		0.075

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-118219464;