16-85072932-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001388359.1(KIAA0513):c.437A>C(p.Asn146Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,461,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: KIAA0513 NM_001388359.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.45

Genes affected

KIAA0513 (HGNC:29058): (KIAA0513) Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30842763).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA0513	NM_001388359.1	c.437A>C	p.Asn146Thr	missense_variant	4/13	ENST00000683363.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA0513	ENST00000683363.1	c.437A>C	p.Asn146Thr	missense_variant	4/13		NM_001388359.1	A1
KIAA0513	ENST00000566428.5	c.437A>C	p.Asn146Thr	missense_variant	4/13	1		A1
KIAA0513	ENST00000567328.6	c.437A>C	p.Asn146Thr	missense_variant	4/8	1
KIAA0513	ENST00000538274.6	c.437A>C	p.Asn146Thr	missense_variant	4/12	2		P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000260 AC: 38 AN: 1461844 Hom.: 0 Cov.: 31 AF XY: 0.0000261 AC XY: 19 AN XY: 727218

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: 0.0000342

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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

Dec 19, 2022

The c.437A>C (p.N146T) alteration is located in exon 4 (coding exon 3) of the KIAA0513 gene. This alteration results from a A to C substitution at nucleotide position 437, causing the asparagine (N) at amino acid position 146 to be replaced by a threonine (T). 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	Benign	0.21
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
Cadd	Uncertain	24
Dann	Uncertain	0.99
DEOGEN2	Benign	0.026	T;.;T;.
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.77	T;T;.;T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.31	T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.3	M;M;M;M
MutationTaster	Benign	0.99	D;D;D;D
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-2.0	N;N;N;D
REVEL	Benign	0.15
Sift	Benign	0.11	T;T;T;D
Sift4G	Benign	0.11	T;T;T;T
Polyphen		0.090	B;.;B;.
Vest4		0.43
MutPred		0.24		Loss of solvent accessibility (P = 0.0769);Loss of solvent accessibility (P = 0.0769);Loss of solvent accessibility (P = 0.0769);Loss of solvent accessibility (P = 0.0769);
MVP		0.53
MPC		0.11
ClinPred		0.95	D
GERP RS		5.5
Varity_R		0.25
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr16-85106538;