5-154011314-T-C

Variant names:

• chr5-154011314-T-C
• rs747686108
• NM_018691.4:c.920A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018691.4(FAM114A2):​c.920A>G​(p.Glu307Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. E307A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM114A2 NM_018691.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.26
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

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.920A>G	p.Glu307Gly	missense	Exon 9 of 14	NP_061161.2	A0A140VKG4
	FAM114A2	NM_001317993.2		c.920A>G	p.Glu307Gly	missense	Exon 10 of 15	NP_001304922.1	Q9NRY5
	FAM114A2	NM_001317994.2		c.920A>G	p.Glu307Gly	missense	Exon 9 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.920A>G	p.Glu307Gly	missense	Exon 9 of 14	ENSP00000341597.4	Q9NRY5
	FAM114A2	ENST00000520667.5	TSL:1	c.920A>G	p.Glu307Gly	missense	Exon 10 of 15	ENSP00000430384.1	Q9NRY5
	FAM114A2	ENST00000522858.5	TSL:1	c.920A>G	p.Glu307Gly	missense	Exon 9 of 14	ENSP00000430489.1	Q9NRY5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		5.3
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Benign	0.12
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.011	D
Polyphen		0.99	D
Vest4		0.58
MutPred		0.12		Loss of methylation at K311 (P = 0.0754)
MVP		0.31
MPC		0.024
ClinPred		0.98	D
GERP RS		4.7
Varity_R		0.25
gMVP		0.22
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.25		Position offset: 6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs747686108; hg19: chr5-153390874;