11-33542722-C-G

Variant names:

• chr11-33542722-C-G
• NM_012194.3:c.1159C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.47

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=0.07993829).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA1549L	NM_012194.3	c.1159C>G	p.Gln387Glu	missense_variant	Exon 2 of 21	ENST00000658780.2	NP_036326.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA1549L	ENST00000658780.2	c.1159C>G	p.Gln387Glu	missense_variant	Exon 2 of 21		NM_012194.3	ENSP00000499430.1
KIAA1549L	ENST00000321505.9	c.268C>G	p.Gln90Glu	missense_variant	Exon 1 of 20	1		ENSP00000315295.4
KIAA1549L	ENST00000265654.6	c.391C>G	p.Gln131Glu	missense_variant	Exon 1 of 11	2		ENSP00000265654.6
KIAA1549L	ENST00000526400.7	c.583+576C>G		intron_variant	Intron 2 of 20	5		ENSP00000433481.3

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

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

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;