1-206201908-T-C

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 8/11 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

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

Verdict is Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM72A	NM_001123168.3	c.118A>G	p.Ile40Val	missense_variant	Exon 1 of 4	ENST00000367128.8	NP_001116640.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM72A	ENST00000367128.8	c.118A>G	p.Ile40Val	missense_variant	Exon 1 of 4	1	NM_001123168.3	ENSP00000356096.3

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000156

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 9

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 01, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.118A>G (p.I40V) alteration is located in exon 1 (coding exon 1) of the FAM72A gene. This alteration results from a A to G substitution at nucleotide position 118, causing the isoleucine (I) at amino acid position 40 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;D;D
MetaRNN	Benign	0.094	T;T;T
PROVEAN	Benign	0.19	N;.;.
Sift	Benign	0.94	T;.;.
Sift4G	Benign	1.0	T;.;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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-206139422;