chr3-138611022-A-C

Variant names:

• chr3-138611022-A-C
• rs964851671
• NM_001033031.2:c.-17+2085A>C

Variant summary

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

The NM_001033030.2(FAIM):​c.65A>C​(p.Asp22Ala) 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. 14/19 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. D22V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAIM NM_001033030.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.321
• Publications: 1 publications found

Genes affected

FAIM (HGNC:18703): (Fas apoptotic inhibitory molecule) The protein encoded by this gene protects against death receptor-triggered apoptosis and regulates B-cell signaling and differentiation. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2011]

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=0.06173426).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033030.2. 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
	FAIM	NM_001033031.2	MANE Select	c.-17+2085A>C		intron	N/A	NP_001028203.1	Q9NVQ4-3
	FAIM	NM_001033030.2		c.65A>C	p.Asp22Ala	missense	Exon 2 of 6	NP_001028202.1	Q9NVQ4-2
	FAIM	NM_001033032.2		c.-23+2085A>C		intron	N/A	NP_001028204.1	Q9NVQ4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAIM	ENST00000360570.8	TSL:3 MANE Select	c.-17+2085A>C		intron	N/A	ENSP00000353775.3	Q9NVQ4-3
	FAIM	ENST00000393035.6	TSL:1	c.-23+2085A>C		intron	N/A	ENSP00000376755.2	Q9NVQ4-1
	FAIM	ENST00000338446.8	TSL:5	c.65A>C	p.Asp22Ala	missense	Exon 2 of 6	ENSP00000342805.4	Q9NVQ4-2

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	0.080
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	3.0
DANN	Benign	0.85
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.00085	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.32
PROVEAN	Benign	0.18	N
REVEL	Benign	0.033
Sift	Benign	0.21	T
Sift4G	Benign	0.14	T
Polyphen		0.0	B
Vest4		0.057
MutPred		0.17		Loss of solvent accessibility (P = 0.0509)
MVP		0.18
MPC		0.25
ClinPred		0.40	T
GERP RS		-3.3
gMVP		0.51
Mutation Taster		=100/0	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: rs964851671; hg19: chr3-138329864;