5-153993001-C-G

Variant names:

• chr5-153993001-C-G
• rs1469292490
• NM_018691.4:c.1493G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018691.4(FAM114A2):​c.1493G>C​(p.Gly498Ala) 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 benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G498V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FAM114A2 NM_018691.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.134
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.01931268).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018691.4. 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
	FAM114A2	NM_018691.4	MANE Select	c.1493G>C	p.Gly498Ala	missense	Exon 14 of 14	NP_061161.2	A0A140VKG4
	FAM114A2	NM_001317993.2		c.1493G>C	p.Gly498Ala	missense	Exon 15 of 15	NP_001304922.1	Q9NRY5
	FAM114A2	NM_001317994.2		c.1493G>C	p.Gly498Ala	missense	Exon 14 of 14	NP_001304923.1	A0A140VKG4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM114A2	ENST00000351797.9	TSL:1 MANE Select	c.1493G>C	p.Gly498Ala	missense	Exon 14 of 14	ENSP00000341597.4	Q9NRY5
	FAM114A2	ENST00000520667.5	TSL:1	c.1493G>C	p.Gly498Ala	missense	Exon 15 of 15	ENSP00000430384.1	Q9NRY5
	FAM114A2	ENST00000522858.5	TSL:1	c.1493G>C	p.Gly498Ala	missense	Exon 14 of 14	ENSP00000430489.1	Q9NRY5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.093
DANN	Benign	0.083
DEOGEN2	Benign	0.0050	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0010	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.20	N
PhyloP100		-0.13
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.56	N
REVEL	Benign	0.011
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.043
MutPred		0.080		Loss of relative solvent accessibility (P = 0.0071)
MVP		0.048
MPC		0.022
ClinPred		0.026	T
GERP RS		-3.0
Varity_R		0.025
gMVP		0.22
Mutation Taster		=100/0	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

dbSNP: rs1469292490; hg19: chr5-153372561;