9-112574243-G-T

Position:

• chr9-112574243-G-T

Variant summary

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

The NM_133465.4(KIAA1958):​c.163G>T​(p.Ala55Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,806 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: 0.0000021 (0 hom.)
• Consequence: KIAA1958 NM_133465.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.57

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/exons	MANE	Protein	UniProt
KIAA1958	NM_133465.4	c.163G>T	p.Ala55Ser	missense_variant	2/4	ENST00000337530.11	NP_597722.1
KIAA1958	NM_001287036.2	c.163G>T	p.Ala55Ser	missense_variant	2/5		NP_001273965.1
KIAA1958	NM_001287038.2	c.163G>T	p.Ala55Ser	missense_variant	2/4		NP_001273967.1
KIAA1958	XM_011518311.3	c.163G>T	p.Ala55Ser	missense_variant	2/3		XP_011516613.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA1958	ENST00000337530.11	c.163G>T	p.Ala55Ser	missense_variant	2/4	1	NM_133465.4	ENSP00000336940.6
KIAA1958	ENST00000536272.5	c.163G>T	p.Ala55Ser	missense_variant	2/5	1		ENSP00000440504.1
KIAA1958	ENST00000374244.3	c.163G>T	p.Ala55Ser	missense_variant	2/3	5		ENSP00000363362.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461806 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727200

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 01, 2022

The c.163G>T (p.A55S) alteration is located in exon 2 (coding exon 1) of the KIAA1958 gene. This alteration results from a G to T substitution at nucleotide position 163, causing the alanine (A) at amino acid position 55 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.068	T;.;.
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.86	D;D;D
M_CAP	Benign	0.0045	T
MetaRNN	Uncertain	0.44	T;T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	0.90	L;L;L
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.070	N;N;N
REVEL	Benign	0.27
Sift	Uncertain	0.0080	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.52
MutPred		0.34		Gain of relative solvent accessibility (P = 0.0215);Gain of relative solvent accessibility (P = 0.0215);Gain of relative solvent accessibility (P = 0.0215);
MVP		0.53
MPC		0.78
ClinPred		0.71	D
GERP RS		6.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.29

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-115336523;