5-153993102-G-C

Variant names:

• chr5-153993102-G-C
• NM_018691.4:c.1392C>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_018691.4(FAM114A2):​c.1392C>G​(p.Asn464Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FAM114A2 NM_018691.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.853

Genes affected

FAM114A2 (HGNC:1333): (family with sequence similarity 114 member A2)

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.746

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM114A2	NM_018691.4	c.1392C>G	p.Asn464Lys	missense_variant	Exon 14 of 14	ENST00000351797.9	NP_061161.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM114A2	ENST00000351797.9	c.1392C>G	p.Asn464Lys	missense_variant	Exon 14 of 14	1	NM_018691.4	ENSP00000341597.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 25, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1392C>G (p.N464K) alteration is located in exon 14 (coding exon 13) of the FAM114A2 gene. This alteration results from a C to G substitution at nucleotide position 1392, causing the asparagine (N) at amino acid position 464 to be replaced by a lysine (K). 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	Pathogenic	0.80
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.53	D;D;D;T
Eigen	Benign	0.15
Eigen_PC	Benign	0.021
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.93	.;.;D;D
M_CAP	Benign	0.031	D
MetaRNN	Pathogenic	0.75	D;D;D;D
MetaSVM	Benign	-0.87	T
MutationAssessor	Pathogenic	2.9	M;M;M;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-5.2	D;D;D;D
REVEL	Benign	0.28
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Uncertain	0.0050	D;D;D;D
Polyphen		1.0	D;D;D;D
Vest4		0.80
MutPred		0.63		Gain of ubiquitination at N464 (P = 0.0203);Gain of ubiquitination at N464 (P = 0.0203);Gain of ubiquitination at N464 (P = 0.0203);.;
MVP		0.20
MPC		0.18
ClinPred		1.0	D
GERP RS		-2.1
Varity_R		0.87
gMVP		0.81

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: chr5-153372662;