Variant 11-33543617-G-A 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.2054G>A(p.Gly685Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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: 6.8e-7 ( 0 hom. )

Consequence

KIAA1549L
NM_012194.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.34

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:

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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=0.14136258).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA1549L	NM_012194.3 linkuse as main transcript	c.2054G>A	p.Gly685Glu	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.2054G>A	p.Gly685Glu	missense_variant	2/21		NM_012194.3	ENSP00000499430.1	A0A590UJI0
KIAA1549L	ENST00000321505.9 linkuse as main transcript	c.1163G>A	p.Gly388Glu	missense_variant	1/20	1		ENSP00000315295.4	Q6ZVL6-1
KIAA1549L	ENST00000265654.6 linkuse as main transcript	c.1286G>A	p.Gly429Glu	missense_variant	1/11	2		ENSP00000265654.6	A0A5F9UK30
KIAA1549L	ENST00000526400.7 linkuse as main transcript	c.584-1150G>A		intron_variant		5		ENSP00000433481.3	H0YDE5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248304

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134784

show subpopulations

Gnomad AFR exome

AF:

0.0000648

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:

6.84e-7

AC:

AN:

1461614

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727090

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Aug 12, 2022

The c.1163G>A (p.G388E) alteration is located in exon 1 (coding exon 1) of the KIAA1549L gene. This alteration results from a G to A substitution at nucleotide position 1163, causing the glycine (G) at amino acid position 388 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

0.099

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.044

T;.

Eigen

Benign

0.19

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.58

T;T

M_CAP

Benign

0.0067

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.6

L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.11

Sift

Uncertain

0.0090

D;D

Sift4G

Uncertain

0.027

D;T

Polyphen

0.99

.;D

Vest4

0.15

MutPred

0.36

Gain of solvent accessibility (P = 0.012);Gain of solvent accessibility (P = 0.012);

MVP

0.24

MPC

0.30

ClinPred

0.21

GERP RS

4.7

Varity_R

0.068

gMVP

0.078

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

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