NM_001394962.1:c.4308G>C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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. 14/21 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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.025248557).
• BS2: High Hemizygotes in GnomAdExome4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394962.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA1210	NM_001394962.1	MANE Select	c.4308G>C	p.Glu1436Asp	missense	Exon 10 of 12	NP_001381891.1	A0A8I5KWH9
	KIAA1210	NM_020721.1		c.4836G>C	p.Glu1612Asp	missense	Exon 12 of 14	NP_065772.1	Q9ULL0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA1210	ENST00000691062.1	MANE Select	c.4308G>C	p.Glu1436Asp	missense	Exon 10 of 12	ENSP00000510348.1	A0A8I5KWH9
	KIAA1210	ENST00000402510.2	TSL:5	c.4836G>C	p.Glu1612Asp	missense	Exon 12 of 14	ENSP00000384670.2	Q9ULL0

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD2 exomes AF: 0.0000397 AC: 7 AN: 176320 AF XY: 0.0000160

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 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

African (AFR) AF: 0.00 AC: 0 AN: 26238

American (AMR) AF: 0.00 AC: 0 AN: 34794

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19256

East Asian (EAS) AF: 0.000332 AC: 10 AN: 30126

South Asian (SAS) AF: 0.00 AC: 0 AN: 53377

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40452

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4120

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 840979

Other (OTH) AF: 0.0000218 AC: 1 AN: 45971

GnomAD4 genome Cov.: 24

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000414 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		-0.016
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
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs777751785; hg19: chrX-118219358;