Genetic Variant KIAA1549L:p.Val401Leu (chr11-33542764-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_012194.3(KIAA1549L):c.1201G>C(p.Val401Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V401M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

KIAA1549L
NM_012194.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.26

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.058214515).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012194.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA1549L	NM_012194.3	MANE Select	c.1201G>C	p.Val401Leu	missense	Exon 2 of 21	NP_036326.3	A0A590UJI0
	KIAA1549L	NM_001410965.1		c.583+618G>C		intron	N/A	NP_001397894.1	H0YDE5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KIAA1549L	ENST00000658780.2	MANE Select	c.1201G>C	p.Val401Leu	missense	Exon 2 of 21	ENSP00000499430.1	A0A590UJI0
KIAA1549L	ENST00000265654.6	TSL:2	c.433G>C	p.Val145Leu	missense	Exon 1 of 11	ENSP00000265654.6	A0A5F9UK30
KIAA1549L	ENST00000526400.7	TSL:5	c.583+618G>C		intron	N/A	ENSP00000433481.3	H0YDE5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000137

AC:

AN:

1461580

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727060

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39680

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53362

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111812

Other (OTH)

AF:

0.00

AC:

AN:

60372

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.077

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.035

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.56

M_CAP

Benign

0.0036

MetaRNN

Benign

0.058

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

PhyloP100

1.3

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.69

REVEL

Benign

0.030

Sift

Benign

0.036

Sift4G

Benign

0.13

Polyphen

0.36

Vest4

0.062

MutPred

0.34

Loss of sheet (P = 0.0315)

MVP

0.061

MPC

0.21

ClinPred

0.18

GERP RS

3.2

PromoterAI

0.0038

Neutral

(source)

Varity_R

0.047

gMVP

0.11

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over