1-206195869-T-C

Variant names:

• chr1-206195869-T-C
• rs1558205862
• NM_001123168.3:c.238A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001123168.3(FAM72A):​c.238A>G​(p.Ile80Val) 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: 18)
  • Exomes 𝑓: 0.000010 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM72A NM_001123168.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.40

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=0.096206605).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM72A	NM_001123168.3	c.238A>G	p.Ile80Val	missense_variant	Exon 3 of 4	ENST00000367128.8	NP_001116640.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM72A	ENST00000367128.8	c.238A>G	p.Ile80Val	missense_variant	Exon 3 of 4	1	NM_001123168.3	ENSP00000356096.3

Frequencies

GnomAD3 genomes Cov.: 18

GnomAD3 exomes AF: 0.00000404 AC: 1 AN: 247528 Hom.: 0 AF XY: 0.00000743 AC XY: 1 AN XY: 134606

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000892

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000103 AC: 15 AN: 1458282 Hom.: 0 Cov.: 30 AF XY: 0.00000965 AC XY: 7 AN XY: 725416

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: 0.0000135

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 18

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.238A>G (p.I80V) alteration is located in exon 3 (coding exon 3) of the FAM72A gene. This alteration results from a A to G substitution at nucleotide position 238, causing the isoleucine (I) at amino acid position 80 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	0.059
BayesDel_noAF	Benign	-0.57
CADD	Benign	14
DANN	Benign	0.26
DEOGEN2	Benign	0.0032	T;.;.;.
LIST_S2	Uncertain	0.90	D;D;D;D
MetaRNN	Benign	0.096	T;T;T;T
PROVEAN	Benign	0.35	N;N;N;.
Sift	Benign	0.97	T;T;T;.
Sift4G	Benign	1.0	T;T;T;.
Vest4		0.072
gMVP		0.089

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

LitVar

Other links and lift over

dbSNP: rs1558205862; hg19: chr1-206145461;