Variant 11-33543340-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_012194.3(KIAA1549L):c.1777C>A(p.His593Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000378 in 1,614,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

KIAA1549L
NM_012194.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.497

Variant links:

Genes affected

KIAA1549L (HGNC:24836): (KIAA1549 like) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

KIAA1549L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.036041796).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA1549L	NM_012194.3 linkuse as main transcript	c.1777C>A	p.His593Asn	missense_variant	2/21	ENST00000658780.2	NP_036326.3	Q6ZVL6Q12914

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KIAA1549L	ENST00000658780.2 linkuse as main transcript	c.1777C>A	p.His593Asn	missense_variant	2/21		NM_012194.3	ENSP00000499430.1	A0A590UJI0
KIAA1549L	ENST00000321505.9 linkuse as main transcript	c.886C>A	p.His296Asn	missense_variant	1/20	1		ENSP00000315295.4	Q6ZVL6-1
KIAA1549L	ENST00000265654.6 linkuse as main transcript	c.1009C>A	p.His337Asn	missense_variant	1/11	2		ENSP00000265654.6	A0A5F9UK30
KIAA1549L	ENST00000526400.7 linkuse as main transcript	c.583+1194C>A		intron_variant		5		ENSP00000433481.3	H0YDE5

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000401

AC:

AN:

249172

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135154

show subpopulations

Gnomad AFR exome

AF:

0.000646

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1461704

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.000687

Gnomad4 AMR exome

AF:

0.0000447

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:

0.00

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000217

AC:

AN:

152348

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000746

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000125

Hom.:

Bravo

AF:

0.000230

ESP6500AA

AF:

0.000512

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000414

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Nov 21, 2024

The c.886C>A (p.H296N) alteration is located in exon 1 (coding exon 1) of the KIAA1549L gene. This alteration results from a C to A substitution at nucleotide position 886, causing the histidine (H) at amino acid position 296 to be replaced by an asparagine (N). 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

0.085

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.034

T;.

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.61

T;T

M_CAP

Benign

0.0051

MetaRNN

Benign

0.036

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;L

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.43

N;N

REVEL

Benign

0.10

Sift

Benign

0.049

D;D

Sift4G

Benign

0.23

T;T

Polyphen

0.37

.;B

Vest4

0.15

MVP

0.12

MPC

0.21

ClinPred

0.026

GERP RS

3.4

Varity_R

0.077

gMVP

0.068

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