Genetic Variant KIAA1549L:p.Ser402Pro (chr11-33542767-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_012194.3(KIAA1549L):c.1204T>C(p.Ser402Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,732 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

KIAA1549L
NM_012194.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.224

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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.054451883).

BP6

Variant 11-33542767-T-C is Benign according to our data. Variant chr11-33542767-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3863775.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA1549L	NM_012194.3 link	c.1204T>C	p.Ser402Pro	missense_variant	Exon 2 of 21	ENST00000658780.2	NP_036326.3	Q6ZVL6Q12914

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KIAA1549L	ENST00000658780.2 link	c.1204T>C	p.Ser402Pro	missense_variant	Exon 2 of 21		NM_012194.3	ENSP00000499430.1	A0A590UJI0
KIAA1549L	ENST00000321505.9 link	c.313T>C	p.Ser105Pro	missense_variant	Exon 1 of 20	1		ENSP00000315295.4	Q6ZVL6-1
KIAA1549L	ENST00000265654.6 link	c.436T>C	p.Ser146Pro	missense_variant	Exon 1 of 11	2		ENSP00000265654.6	A0A5F9UK30
KIAA1549L	ENST00000526400.7 link	c.583+621T>C		intron_variant	Intron 2 of 20	5		ENSP00000433481.3	H0YDE5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

248420

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

134814

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:

0.0000267

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461594

Hom.:

Cov.:

AF XY:

0.00000550

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:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152138

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000828

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Feb 13, 2025

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.51

CADD

Benign

8.0

DANN

Benign

0.39

DEOGEN2

Benign

0.036

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.39

T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.054

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.63

N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.40

N;N

REVEL

Benign

0.025

Sift

Benign

0.30

T;T

Sift4G

Benign

0.25

T;T

Polyphen

0.0

.;B

Vest4

0.13

MutPred

0.44

Loss of catalytic residue at S105 (P = 0.0026);Loss of catalytic residue at S105 (P = 0.0026);

MVP

0.081

MPC

0.22

ClinPred

0.017

GERP RS

0.0098

Varity_R

0.048

gMVP

0.10

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