rs138154810

Variant names:

• chr22-45203927-C-G
• rs138154810
• NM_001009880.2:c.575G>C

Your query was ambiguous. Multiple possible variants found:

• chr22-45203927-C-G
• chr22-45203927-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001009880.2(KIAA0930):​c.575G>C​(p.Ser192Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S192N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KIAA0930 NM_001009880.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.45
• Publications: 0 publications found

Genes affected

KIAA0930 (HGNC:1314): (KIAA0930)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39718896).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0930	NM_001009880.2	c.575G>C	p.Ser192Thr	missense_variant	Exon 6 of 10	ENST00000336156.10	NP_001009880.1
KIAA0930	NM_015264.2	c.590G>C	p.Ser197Thr	missense_variant	Exon 6 of 10		NP_056079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA0930	ENST00000336156.10	c.575G>C	p.Ser192Thr	missense_variant	Exon 6 of 10	1	NM_001009880.2	ENSP00000336720.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461808 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727208

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111956

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	0.00050	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	25
DANN	Benign	0.93
DEOGEN2	Benign	0.033	T;T;.;.
Eigen	Benign	-0.087
Eigen_PC	Benign	0.091
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D;D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.40	T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.1	L;.;.;.
PhyloP100		7.5
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.73	N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.41	T;T;T;T
Sift4G	Benign	0.45	T;T;T;T
Polyphen		0.0010	B;.;B;.
Vest4		0.69
MutPred		0.43		Loss of stability (P = 0.0434);.;.;.;
MVP		0.043
MPC		0.70
ClinPred		0.81	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.22
Mutation Taster		=62/38	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs138154810; hg19: chr22-45599808;