NM_014367.4:c.316C>G

Variant names:

• chr3-122407333-C-G
• NM_014367.4:c.316C>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_014367.4(FAM162A):​c.316C>G​(p.Leu106Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: FAM162A NM_014367.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.58
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03742647).
• BP6: Variant 3-122407333-C-G is Benign according to our data. Variant chr3-122407333-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2244653.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014367.4. 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
	FAM162A	NM_014367.4	MANE Select	c.316C>G	p.Leu106Val	missense	Exon 4 of 5	NP_055182.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM162A	ENST00000477892.5	TSL:1 MANE Select	c.316C>G	p.Leu106Val	missense	Exon 4 of 5	ENSP00000419088.1	Q96A26
	FAM162A	ENST00000692876.1		c.334C>G	p.Leu112Val	missense	Exon 5 of 6	ENSP00000509253.1	A0A8I5KUL7
	FAM162A	ENST00000232125.9	TSL:2	c.286C>G	p.Leu96Val	missense	Exon 5 of 6	ENSP00000232125.5	F8W7Q4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461816 Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4 AN XY: 727210

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.000224 AC: 10 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111970

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.071
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.0010
DANN	Benign	0.50
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-2.3
Eigen_PC	Benign	-2.4
FATHMM_MKL	Benign	0.0074	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.10	N
PhyloP100		-2.6
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.040	N
REVEL	Benign	0.015
Sift	Benign	0.75	T
Sift4G	Benign	0.81	T
Polyphen		0.0030	B
Vest4		0.13
MutPred		0.34		Gain of sheet (P = 0.0344)
MVP		0.16
MPC		0.24
ClinPred		0.021	T
GERP RS		-11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.018
gMVP		0.67
Mutation Taster		=90/10	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

hg19: chr3-122126180; COSMIC: COSV51658747; COSMIC: COSV51658747;