NM_012194.3:c.904G>A

Variant names:

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

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>A​(p.Ala302Thr) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KIAA1549L NM_012194.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.04131654).

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>A	p.Ala302Thr	missense	Exon 2 of 21	NP_036326.3	A0A590UJI0
	KIAA1549L	NM_001410965.1		c.583+321G>A		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>A	p.Ala302Thr	missense	Exon 2 of 21	ENSP00000499430.1	A0A590UJI0
	KIAA1549L	ENST00000265654.6	TSL:2	c.136G>A	p.Ala46Thr	missense	Exon 1 of 11	ENSP00000265654.6	A0A5F9UK30
	KIAA1549L	ENST00000526400.7	TSL:5	c.583+321G>A		intron	N/A	ENSP00000433481.3	H0YDE5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	7.4
DANN	Benign	0.90
DEOGEN2	Benign	0.021	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.11
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.15	N
REVEL	Benign	0.016
Sift	Uncertain	0.022	D
Sift4G	Benign	0.23	T
Polyphen		0.0	B
Vest4		0.038
MutPred		0.24		Gain of relative solvent accessibility (P = 0.0479)
MVP		0.030
MPC		0.17
ClinPred		0.061	T
GERP RS		0.77
PromoterAI		0.018	Neutral
Varity_R		0.031
gMVP		0.077
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;