11-33542722-C-G

Variant summary

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

The NM_012194.3(KIAA1549L):​c.1159C>G​(p.Gln387Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,658 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

KIAA1549L
NM_012194.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.47
Variant links:
Genes affected
KIAA1549L (HGNC:24836): (KIAA1549 like) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.07993829).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KIAA1549LNM_012194.3 linkc.1159C>G p.Gln387Glu missense_variant Exon 2 of 21 ENST00000658780.2 NP_036326.3 Q6ZVL6Q12914

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KIAA1549LENST00000658780.2 linkc.1159C>G p.Gln387Glu missense_variant Exon 2 of 21 NM_012194.3 ENSP00000499430.1 A0A590UJI0
KIAA1549LENST00000321505.9 linkc.268C>G p.Gln90Glu missense_variant Exon 1 of 20 1 ENSP00000315295.4 Q6ZVL6-1
KIAA1549LENST00000265654.6 linkc.391C>G p.Gln131Glu missense_variant Exon 1 of 11 2 ENSP00000265654.6 A0A5F9UK30
KIAA1549LENST00000526400.7 linkc.583+576C>G intron_variant Intron 2 of 20 5 ENSP00000433481.3 H0YDE5

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461658
Hom.:
0
Cov.:
38
AF XY:
0.00
AC XY:
0
AN XY:
727110
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:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 21, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.268C>G (p.Q90E) alteration is located in exon 1 (coding exon 1) of the KIAA1549L gene. This alteration results from a C to G substitution at nucleotide position 268, causing the glutamine (Q) at amino acid position 90 to be replaced by a glutamic acid (E). 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
0.076
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
15
DANN
Benign
0.87
DEOGEN2
Benign
0.033
T;.
Eigen
Benign
-0.80
Eigen_PC
Benign
-0.78
FATHMM_MKL
Benign
0.32
N
LIST_S2
Benign
0.53
T;T
M_CAP
Benign
0.0062
T
MetaRNN
Benign
0.080
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.97
L;L
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-0.44
N;N
REVEL
Benign
0.069
Sift
Uncertain
0.011
D;D
Sift4G
Benign
0.26
T;T
Polyphen
0.56
.;P
Vest4
0.11
MutPred
0.26
Gain of helix (P = 0.062);Gain of helix (P = 0.062);
MVP
0.14
MPC
0.21
ClinPred
0.11
T
GERP RS
4.1
Varity_R
0.062
gMVP
0.061

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: chr11-33564268; API