Variant chr16-85077494-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001388359.1(KIAA0513):c.644C>T(p.Ser215Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,614,086 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: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

KIAA0513
NM_001388359.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.48

Variant links:

Genes affected

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

KIAA0513 links:

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ACMG classification

Classification made for transcript

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=0.29952085).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0513	NM_001388359.1 linkuse as main transcript	c.644C>T	p.Ser215Phe	missense_variant	6/13	ENST00000683363.1	NP_001375288.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0513	ENST00000683363.1 linkuse as main transcript	c.644C>T	p.Ser215Phe	missense_variant	6/13		NM_001388359.1	ENSP00000507772	A1	O60268-1
KIAA0513	ENST00000566428.5 linkuse as main transcript	c.644C>T	p.Ser215Phe	missense_variant	6/13	1		ENSP00000457408	A1	O60268-1
KIAA0513	ENST00000567328.6 linkuse as main transcript	c.644C>T	p.Ser215Phe	missense_variant	6/8	1		ENSP00000455544		O60268-2
KIAA0513	ENST00000538274.6 linkuse as main transcript	c.644C>T	p.Ser215Phe	missense_variant	6/12	2		ENSP00000446439	P4	O60268-3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000150

AC:

AN:

1461856

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.0000189

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2024

The c.644C>T (p.S215F) alteration is located in exon 6 (coding exon 5) of the KIAA0513 gene. This alteration results from a C to T substitution at nucleotide position 644, causing the serine (S) at amino acid position 215 to be replaced by a phenylalanine (F). 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

Uncertain

0.47

BayesDel_addAF

Benign

-0.045

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.031

T;.;T;.;T

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.96

D;D;.;D;D

M_CAP

Benign

0.028

MetaRNN

Benign

0.30

T;T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.5

M;M;M;M;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.0

N;N;N;N;N

REVEL

Benign

0.21

Sift

Uncertain

0.0040

D;D;D;D;D

Sift4G

Uncertain

0.017

D;D;D;D;D

Polyphen

1.0

D;.;D;.;.

Vest4

0.66

MutPred

0.47

Loss of disorder (P = 0.004);Loss of disorder (P = 0.004);Loss of disorder (P = 0.004);Loss of disorder (P = 0.004);.;

MVP

0.69

MPC

0.11

ClinPred

0.65

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.17

gMVP

0.54

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over