NM_001123168.3:c.118A>G

Variant names:

• chr1-206201908-T-C
• NM_001123168.3:c.118A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001123168.3(FAM72A):​c.118A>G​(p.Ile40Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 8/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 9)
  • Exomes 𝑓: 0.0000092 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM72A NM_001123168.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.97
• Publications: 0 publications found

Genes affected

FAM72A (HGNC:24044): (family with sequence similarity 72 member A) Predicted to act upstream of or within negative regulation of brain-derived neurotrophic factor-activated receptor activity and positive regulation of apoptotic process. Located in cytosol and intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.093700945).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001123168.3. 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
	FAM72A	NM_001123168.3	MANE Select	c.118A>G	p.Ile40Val	missense	Exon 1 of 4	NP_001116640.1	Q5TYM5-1
	FAM72A	NM_001385240.1		c.118A>G	p.Ile40Val	missense	Exon 3 of 6	NP_001372169.1	Q5TYM5-1
	FAM72A	NM_001385241.1		c.118A>G	p.Ile40Val	missense	Exon 3 of 6	NP_001372170.1	Q5TYM5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM72A	ENST00000367128.8	TSL:1 MANE Select	c.118A>G	p.Ile40Val	missense	Exon 1 of 4	ENSP00000356096.3	Q5TYM5-1
	FAM72A	ENST00000341209.9	TSL:1	c.32+86A>G		intron	N/A	ENSP00000340661.5	Q5TYM5-2
	FAM72A	ENST00000931113.1		c.118A>G	p.Ile40Val	missense	Exon 1 of 4	ENSP00000601172.1

Frequencies

GnomAD3 genomes Cov.: 9

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000916 AC: 4 AN: 436452 Hom.: 0 Cov.: 0 AF XY: 0.0000131 AC XY: 3 AN XY: 228512

African (AFR) AF: 0.00 AC: 0 AN: 11968

American (AMR) AF: 0.00 AC: 0 AN: 18530

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13182

East Asian (EAS) AF: 0.00 AC: 0 AN: 30120

South Asian (SAS) AF: 0.00 AC: 0 AN: 45436

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1892

European-Non Finnish (NFE) AF: 0.0000156 AC: 4 AN: 255726

Other (OTH) AF: 0.00 AC: 0 AN: 24988

GnomAD4 genome Cov.: 9

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	0.067
BayesDel_noAF	Benign	-0.58
CADD	Benign	18
DANN	Benign	0.88
DEOGEN2	Benign	0.0041	T
LIST_S2	Uncertain	0.87	D
MetaRNN	Benign	0.094	T
PhyloP100		2.0
PROVEAN	Benign	0.19	N
Sift	Benign	0.94	T
Sift4G	Benign	1.0	T
Vest4		0.095
gMVP		0.13

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

hg19: chr1-206139422;