rs10981449

Variant names:

• chr9-112574056-G-A
• rs10981449
• NM_133465.4:c.-24-1G>A

Variant summary

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

The NM_133465.4(KIAA1958):​c.-24-1G>A variant causes a splice acceptor, intron change. The variant allele was found at a frequency of 0.000000774 in 1,291,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: KIAA1958 NM_133465.4 splice_acceptor, intron
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.71

Genes affected

KIAA1958 (HGNC:23427): (KIAA1958)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA1958	NM_133465.4	c.-24-1G>A		splice_acceptor_variant, intron_variant	Intron 1 of 3	ENST00000337530.11	NP_597722.1
KIAA1958	NM_001287036.2	c.-24-1G>A		splice_acceptor_variant, intron_variant	Intron 1 of 4		NP_001273965.1
KIAA1958	NM_001287038.2	c.-24-1G>A		splice_acceptor_variant, intron_variant	Intron 1 of 3		NP_001273967.1
KIAA1958	XM_011518311.3	c.-24-1G>A		splice_acceptor_variant, intron_variant	Intron 1 of 2		XP_011516613.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA1958	ENST00000337530.11	c.-24-1G>A		splice_acceptor_variant, intron_variant	Intron 1 of 3	1	NM_133465.4	ENSP00000336940.6
KIAA1958	ENST00000536272.5	c.-24-1G>A		splice_acceptor_variant, intron_variant	Intron 1 of 4	1		ENSP00000440504.1
KIAA1958	ENST00000374244.3	c.-24-1G>A		splice_acceptor_variant, intron_variant	Intron 1 of 2	5		ENSP00000363362.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.74e-7 AC: 1 AN: 1291596 Hom.: 0 Cov.: 19 AF XY: 0.00000157 AC XY: 1 AN XY: 638898

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000101

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000628 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	33
DANN	Uncertain	0.99
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.93
SpliceAI score (max)		0.90		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.35		Position offset: 2
DS_AL_spliceai		0.90		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10981449; hg19: chr9-115336336;