chr12-49890715-A-G

Variant names:

• chr12-49890715-A-G
• NM_012306.4:c.493T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_012306.4(FAIM2):​c.493T>C​(p.Phe165Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAIM2 NM_012306.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.51
• Publications: 0 publications found

Genes affected

FAIM2 (HGNC:17067): (Fas apoptotic inhibitory molecule 2) Involved in regulation of neuron apoptotic process. Acts upstream of or within negative regulation of extrinsic apoptotic signaling pathway via death domain receptors. Located in membrane raft. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012306.4. 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
	FAIM2	NM_012306.4	MANE Select	c.493T>C	p.Phe165Leu	missense	Exon 7 of 12	NP_036438.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAIM2	ENST00000320634.8	TSL:1 MANE Select	c.493T>C	p.Phe165Leu	missense	Exon 7 of 12	ENSP00000321951.3	Q9BWQ8-1
	FAIM2	ENST00000947305.1		c.511T>C	p.Phe171Leu	missense	Exon 7 of 12	ENSP00000617364.1
	FAIM2	ENST00000947304.1		c.490T>C	p.Phe164Leu	missense	Exon 7 of 12	ENSP00000617363.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.42	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.22	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-0.33	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		7.5
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.36
Sift	Benign	0.036	D
Sift4G	Benign	0.11	T
Polyphen		0.85	P
Vest4		0.56
MutPred		0.51		Gain of catalytic residue at F165 (P = 0)
MVP		0.35
MPC		0.92
ClinPred		0.99	D
GERP RS		4.8
Varity_R		0.41
gMVP		0.93
Mutation Taster		=53/47	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr12-50284498;