9-112574493-A-G

Variant names:

• chr9-112574493-A-G
• rs189232038
• NM_133465.4:c.413A>G

Variant summary

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

The NM_133465.4(KIAA1958):​c.413A>G​(p.Tyr138Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. Y138F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KIAA1958 NM_133465.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.82
• Publications: 0 publications found

Genes affected

KIAA1958 (HGNC:23427): (KIAA1958)

ACMG classification

Our verdict: Uncertain_significance. The variant received 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.413A>G	p.Tyr138Cys	missense_variant	Exon 2 of 4	ENST00000337530.11	NP_597722.1
KIAA1958	NM_001287036.2	c.413A>G	p.Tyr138Cys	missense_variant	Exon 2 of 5		NP_001273965.1
KIAA1958	NM_001287038.2	c.413A>G	p.Tyr138Cys	missense_variant	Exon 2 of 4		NP_001273967.1
KIAA1958	XM_011518311.3	c.413A>G	p.Tyr138Cys	missense_variant	Exon 2 of 3		XP_011516613.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA1958	ENST00000337530.11	c.413A>G	p.Tyr138Cys	missense_variant	Exon 2 of 4	1	NM_133465.4	ENSP00000336940.6
KIAA1958	ENST00000536272.5	c.413A>G	p.Tyr138Cys	missense_variant	Exon 2 of 5	1		ENSP00000440504.1
KIAA1958	ENST00000374244.3	c.413A>G	p.Tyr138Cys	missense_variant	Exon 2 of 3	5		ENSP00000363362.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.096	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.052	T;.;.
Eigen	Uncertain	0.62
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.45	T;T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	0.90	L;L;L
PhyloP100		5.8
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.53	N;N;N
REVEL	Benign	0.25
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.59
MutPred		0.19		Loss of phosphorylation at Y138 (P = 0.0182);Loss of phosphorylation at Y138 (P = 0.0182);Loss of phosphorylation at Y138 (P = 0.0182);
MVP		0.84
MPC		0.36
ClinPred		0.67	D
GERP RS		6.1
Varity_R		0.26
gMVP		0.21
Mutation Taster		=67/33	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: rs189232038; hg19: chr9-115336773; COSMIC: COSV61722803;