11-33542467-G-C

Variant names:

• chr11-33542467-G-C
• rs760366531
• NM_012194.3:c.904G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012194.3(KIAA1549L):​c.904G>C​(p.Ala302Pro) 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A302T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KIAA1549L NM_012194.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109
• 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: 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=0.024877727).

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.904G>C	p.Ala302Pro	missense	Exon 2 of 21	NP_036326.3	A0A590UJI0
	KIAA1549L	NM_001410965.1		c.583+321G>C		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.904G>C	p.Ala302Pro	missense	Exon 2 of 21	ENSP00000499430.1	A0A590UJI0
	KIAA1549L	ENST00000265654.6	TSL:2	c.136G>C	p.Ala46Pro	missense	Exon 1 of 11	ENSP00000265654.6	A0A5F9UK30
	KIAA1549L	ENST00000526400.7	TSL:5	c.583+321G>C		intron	N/A	ENSP00000433481.3	H0YDE5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.16
DANN	Benign	0.096
DEOGEN2	Benign	0.021	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0063	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.025	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.90	N
PhyloP100		-0.11
PrimateAI	Benign	0.27	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.033
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.035
MutPred		0.27		Gain of disorder (P = 0.043)
MVP		0.055
MPC		0.22
ClinPred		0.023	T
GERP RS		0.77
PromoterAI		0.011	Neutral
Varity_R		0.046
gMVP		0.072
Mutation Taster		=99/1	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

dbSNP: rs760366531; hg19: chr11-33564013;