X-119085395-C-G

Variant names:

• chrX-119085395-C-G
• rs777751785
• NM_001394962.1:c.4308G>C

Variant summary

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

The NM_001394962.1(KIAA1210):​c.4308G>C​(p.Glu1436Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00001 in 1,095,313 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.000010 (0 hom. 3 hem.)
• Consequence: KIAA1210 NM_001394962.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0160

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=0.025248557).
• BS2: High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA1210	NM_001394962.1	c.4308G>C	p.Glu1436Asp	missense_variant	Exon 10 of 12	ENST00000691062.1	NP_001381891.1
KIAA1210	NM_020721.1	c.4836G>C	p.Glu1612Asp	missense_variant	Exon 12 of 14		NP_065772.1
KIAA1210	XM_017029688.3	c.4353G>C	p.Glu1451Asp	missense_variant	Exon 10 of 12		XP_016885177.1
KIAA1210	XM_017029689.3	c.4155G>C	p.Glu1385Asp	missense_variant	Exon 9 of 11		XP_016885178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA1210	ENST00000691062.1	c.4308G>C	p.Glu1436Asp	missense_variant	Exon 10 of 12		NM_001394962.1	ENSP00000510348.1
KIAA1210	ENST00000402510.2	c.4836G>C	p.Glu1612Asp	missense_variant	Exon 12 of 14	5		ENSP00000384670.2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD3 exomes AF: 0.0000397 AC: 7 AN: 176320 Hom.: 0 AF XY: 0.0000160 AC XY: 1 AN XY: 62562

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000533

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000100 AC: 11 AN: 1095313 Hom.: 0 Cov.: 30 AF XY: 0.00000831 AC XY: 3 AN XY: 361033

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000332

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000218

GnomAD4 genome Cov.: 24

Bravo AF: 0.0000340

ExAC AF: 0.0000414 AC: 5

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 05, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4836G>C (p.E1612D) alteration is located in exon 12 (coding exon 12) of the KIAA1210 gene. This alteration results from a G to C substitution at nucleotide position 4836, causing the glutamic acid (E) at amino acid position 1612 to be replaced by an aspartic acid (D). 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	0.23
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.93
CADD	Benign	11
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0074	T
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.025	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.058
Sift	Benign	0.070	T
Sift4G	Benign	0.10	T
Polyphen		0.70	P
Vest4		0.13
MutPred		0.11		Loss of methylation at K1611 (P = 0.1084);
MVP		0.11
MPC		0.033
ClinPred		0.066	T
GERP RS		-0.49
Varity_R		0.097
gMVP		0.049

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: rs777751785; hg19: chrX-118219358;