12-49903887-T-A

Variant names:

• chr12-49903887-T-A
• rs706795
• NM_012306.4:c.-95A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012306.4(FAIM2):​c.-95A>T variant causes a 5 prime UTR premature start codon gain 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAIM2 NM_012306.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.32
• 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]

LINC02395 (HGNC:53322): (long intergenic non-protein coding RNA 2395)

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 (BayesDel_noAF=-0.32).

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.-95A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 12	NP_036438.2
	FAIM2	NM_012306.4	MANE Select	c.-95A>T		5_prime_UTR	Exon 1 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.-95A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 12	ENSP00000321951.3	Q9BWQ8-1
	FAIM2	ENST00000320634.8	TSL:1 MANE Select	c.-95A>T		5_prime_UTR	Exon 1 of 12	ENSP00000321951.3	Q9BWQ8-1
	FAIM2	ENST00000947305.1		c.-95A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 12	ENSP00000617364.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1191964 Hom.: 0 Cov.: 16 AF XY: 0.00 AC XY: 0 AN XY: 586240

African (AFR) AF: 0.00 AC: 0 AN: 25514

American (AMR) AF: 0.00 AC: 0 AN: 24006

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18628

East Asian (EAS) AF: 0.00 AC: 0 AN: 31998

South Asian (SAS) AF: 0.00 AC: 0 AN: 63246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43812

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3456

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 931190

Other (OTH) AF: 0.00 AC: 0 AN: 50114

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	21
DANN	Benign	0.95
PhyloP100		2.3
PromoterAI		-0.14	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs706795; hg19: chr12-50297670;