Variant 11-33542780-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012194.3(KIAA1549L):c.1217T>G(p.Phe406Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,578 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: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

KIAA1549L
NM_012194.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.804

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.115315914).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA1549L	NM_012194.3 linkuse as main transcript	c.1217T>G	p.Phe406Cys	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.1217T>G	p.Phe406Cys	missense_variant	2/21		NM_012194.3	ENSP00000499430.1	A0A590UJI0
KIAA1549L	ENST00000321505.9 linkuse as main transcript	c.326T>G	p.Phe109Cys	missense_variant	1/20	1		ENSP00000315295.4	Q6ZVL6-1
KIAA1549L	ENST00000265654.6 linkuse as main transcript	c.449T>G	p.Phe150Cys	missense_variant	1/11	2		ENSP00000265654.6	A0A5F9UK30
KIAA1549L	ENST00000526400.7 linkuse as main transcript	c.583+634T>G		intron_variant		5		ENSP00000433481.3	H0YDE5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248330

Hom.:

AF XY:

0.00000742

AC XY:

AN XY:

134782

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00000889

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461578

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727072

show subpopulations

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Jul 02, 2024

The c.326T>G (p.F109C) alteration is located in exon 1 (coding exon 1) of the KIAA1549L gene. This alteration results from a T to G substitution at nucleotide position 326, causing the phenylalanine (F) at amino acid position 109 to be replaced by a cysteine (C). 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

0.16

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.047

T;.

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.44

T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.070

Sift

Uncertain

0.018

D;D

Sift4G

Uncertain

0.039

D;D

Polyphen

1.0

.;D

Vest4

0.38

MutPred

0.30

Loss of stability (P = 0.0213);Loss of stability (P = 0.0213);

MVP

0.11

MPC

0.45

ClinPred

0.094

GERP RS

0.098

Varity_R

0.056

gMVP

0.099

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