NM_012194.3:c.1159C>G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 16/21 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
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07993829).

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.1159C>G	p.Gln387Glu	missense	Exon 2 of 21	NP_036326.3	A0A590UJI0
	KIAA1549L	NM_001410965.1		c.583+576C>G		intron	N/A	NP_001397894.1	H0YDE5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA1549L	ENST00000658780.2	MANE Select	c.1159C>G	p.Gln387Glu	missense	Exon 2 of 21	ENSP00000499430.1	A0A590UJI0
	KIAA1549L	ENST00000265654.6	TSL:2	c.391C>G	p.Gln131Glu	missense	Exon 1 of 11	ENSP00000265654.6	A0A5F9UK30
	KIAA1549L	ENST00000526400.7	TSL:5	c.583+576C>G		intron	N/A	ENSP00000433481.3	H0YDE5

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

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111844

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 33

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L
PhyloP100		1.5
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.069
Sift	Uncertain	0.011	D
Sift4G	Benign	0.26	T
Polyphen		0.56	P
Vest4		0.11
MutPred		0.26		Gain of helix (P = 0.062)
MVP		0.14
MPC		0.21
ClinPred		0.11	T
GERP RS		4.1
PromoterAI		-0.00050	Neutral
Varity_R		0.062
gMVP		0.061
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

hg19: chr11-33564268;