11-33542816-C-T

Position:

• chr11-33542816-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012194.3(KIAA1549L):​c.1253C>T​(p.Pro418Leu) 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. 14/20 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)
• Consequence: KIAA1549L NM_012194.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.742

Genes affected

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

ACMG classification

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=0.06901318).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA1549L	NM_012194.3	c.1253C>T	p.Pro418Leu	missense_variant	2/21	ENST00000658780.2	NP_036326.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA1549L	ENST00000658780.2	c.1253C>T	p.Pro418Leu	missense_variant	2/21		NM_012194.3	ENSP00000499430.1
KIAA1549L	ENST00000321505.9	c.362C>T	p.Pro121Leu	missense_variant	1/20	1		ENSP00000315295.4
KIAA1549L	ENST00000265654.6	c.485C>T	p.Pro162Leu	missense_variant	1/11	2		ENSP00000265654.6
KIAA1549L	ENST00000526400.7	c.583+670C>T		intron_variant		5		ENSP00000433481.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2024

The c.362C>T (p.P121L) alteration is located in exon 1 (coding exon 1) of the KIAA1549L gene. This alteration results from a C to T substitution at nucleotide position 362, causing the proline (P) at amino acid position 121 to be replaced by a leucine (L). 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	0.063
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	T;.
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.60	T;T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.069	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;N
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.20	N;N
REVEL	Benign	0.020
Sift	Uncertain	0.028	D;D
Sift4G	Benign	0.13	T;T
Polyphen		0.0040	.;B
Vest4		0.067
MutPred		0.25		Loss of loop (P = 0.0203);Loss of loop (P = 0.0203);
MVP		0.14
MPC		0.18
ClinPred		0.22	T
GERP RS		3.5
Varity_R		0.035
gMVP		0.15

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: chr11-33564362;