rs1456173544

Variant names:

• chr22-45199989-G-C
• rs1456173544
• NM_001009880.2:c.899C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001009880.2(KIAA0930):​c.899C>G​(p.Pro300Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,456,122 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: KIAA0930 NM_001009880.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.37
• Publications: 0 publications found

Genes affected

KIAA0930 (HGNC:1314): (KIAA0930)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001009880.2. 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
	KIAA0930	NM_001009880.2	MANE Select	c.899C>G	p.Pro300Arg	missense	Exon 8 of 10	NP_001009880.1	Q6ICG6-1
	KIAA0930	NM_015264.2		c.914C>G	p.Pro305Arg	missense	Exon 8 of 10	NP_056079.1	Q6ICG6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0930	ENST00000336156.10	TSL:1 MANE Select	c.899C>G	p.Pro300Arg	missense	Exon 8 of 10	ENSP00000336720.4	Q6ICG6-1
	KIAA0930	ENST00000391627.6	TSL:1	c.797C>G	p.Pro266Arg	missense	Exon 8 of 10	ENSP00000375485.2	Q6ICG6-3
	KIAA0930	ENST00000488038.5	TSL:1	n.1185C>G		non_coding_transcript_exon	Exon 7 of 9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000817 AC: 2 AN: 244730 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000203

Gnomad EAS 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: 0.00000343 AC: 5 AN: 1456122 Hom.: 0 Cov.: 32 AF XY: 0.00000276 AC XY: 2 AN XY: 724244

African (AFR) AF: 0.00 AC: 0 AN: 33096

American (AMR) AF: 0.00 AC: 0 AN: 44004

Ashkenazi Jewish (ASJ) AF: 0.000116 AC: 3 AN: 25972

East Asian (EAS) AF: 0.00 AC: 0 AN: 38938

South Asian (SAS) AF: 0.00 AC: 0 AN: 85588

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53362

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1109260

Other (OTH) AF: 0.00 AC: 0 AN: 60164

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000508 Hom.: 0

Bravo AF: 0.00000756

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	Uncertain	0.40
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.34
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.031	T
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	0.97	L
PhyloP100		9.4
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.61	N
REVEL	Uncertain	0.34
Sift	Benign	0.30	T
Sift4G	Benign	0.62	T
Polyphen		0.99	D
Vest4		0.91
MutPred		0.34		Gain of MoRF binding (P = 0.0073)
MVP		0.26
MPC		1.4
ClinPred		0.66	D
GERP RS		5.0
Varity_R		0.13
gMVP		0.81
Mutation Taster		=46/54	disease causing

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: rs1456173544; hg19: chr22-45595870;