NM_012306.4:c.327C>T

Variant names:

• chr12-49897572-G-A
• rs147548351
• NM_012306.4:c.327C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_012306.4(FAIM2):​c.327C>T​(p.Ile109Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000954 in 1,614,036 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00064 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00099 (0 hom.)
• Consequence: FAIM2 NM_012306.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.556
• 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 12-49897572-G-A is Benign according to our data. Variant chr12-49897572-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2642972.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.556 with no splicing effect.

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.327C>T	p.Ile109Ile	synonymous	Exon 4 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.327C>T	p.Ile109Ile	synonymous	Exon 4 of 12	ENSP00000321951.3	Q9BWQ8-1
	FAIM2	ENST00000947305.1		c.345C>T	p.Ile115Ile	synonymous	Exon 4 of 12	ENSP00000617364.1
	FAIM2	ENST00000947304.1		c.327C>T	p.Ile109Ile	synonymous	Exon 4 of 12	ENSP00000617363.1

Frequencies

GnomAD3 genomes AF: 0.000644 AC: 98 AN: 152206 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000911

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000598 AC: 150 AN: 250734 AF XY: 0.000634

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.00101

Gnomad ASJ exome AF: 0.0000995

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000884

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000986 AC: 1441 AN: 1461712 Hom.: 0 Cov.: 31 AF XY: 0.000960 AC XY: 698 AN XY: 727160

African (AFR) AF: 0.000239 AC: 8 AN: 33478

American (AMR) AF: 0.000917 AC: 41 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26126

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.000232 AC: 20 AN: 86230

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53410

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.00118 AC: 1311 AN: 1111904

Other (OTH) AF: 0.000894 AC: 54 AN: 60390

GnomAD4 genome AF: 0.000643 AC: 98 AN: 152324 Hom.: 1 Cov.: 32 AF XY: 0.000604 AC XY: 45 AN XY: 74486

African (AFR) AF: 0.000241 AC: 10 AN: 41572

American (AMR) AF: 0.00137 AC: 21 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000911 AC: 62 AN: 68020

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000735 Hom.: 0

Bravo AF: 0.000759

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00120

EpiControl AF: 0.00148

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	13
DANN	Benign	0.78
PhyloP100		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs147548351; hg19: chr12-50291355; COSMIC: COSV57740022; COSMIC: COSV57740022;