3-122384276-T-G

Position:

• chr3-122384276-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014367.4(FAM162A):​c.11T>G​(p.Leu4Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,426,392 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: FAM162A NM_014367.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.85

Genes affected

FAM162A (HGNC:17865): (family with sequence similarity 162 member A) Involved in several processes, including activation of cysteine-type endopeptidase activity involved in apoptotic process; cellular response to hypoxia; and positive regulation of release of cytochrome c from mitochondria. Located in cytosol and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM162A	NM_014367.4	c.11T>G	p.Leu4Arg	missense_variant	1/5	ENST00000477892.5	NP_055182.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM162A	ENST00000477892.5	c.11T>G	p.Leu4Arg	missense_variant	1/5	1	NM_014367.4	ENSP00000419088	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.01e-7 AC: 1 AN: 1426392 Hom.: 0 Cov.: 31 AF XY: 0.00000142 AC XY: 1 AN XY: 706056

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: 9.13e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2022

The c.11T>G (p.L4R) alteration is located in exon 1 (coding exon 1) of the FAM162A gene. This alteration results from a T to G substitution at nucleotide position 11, causing the leucine (L) at amino acid position 4 to be replaced by an arginine (R). 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	0.11
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.030	T;T
Eigen	Benign	0.18
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.46	T;T
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.64	D;D
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.4	M;.
MutationTaster	Benign	1.0	D;N;N
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.14
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		0.97	D;D
Vest4		0.73
MutPred		0.29		Gain of MoRF binding (P = 1e-04);Gain of MoRF binding (P = 1e-04);
MVP		0.56
MPC		1.0
ClinPred		0.97	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.63
gMVP		0.39

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: chr3-122103123;