chr5-153997852-T-G

Variant names:

• chr5-153997852-T-G
• rs373121338
• NM_018691.4:c.1280A>C

Variant summary

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

The NM_018691.4(FAM114A2):​c.1280A>C​(p.Glu427Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000117 in 1,451,906 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: 0.000012 (0 hom.)
• Consequence: FAM114A2 NM_018691.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.73
• 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.1280A>C	p.Glu427Ala	missense	Exon 12 of 14	NP_061161.2	A0A140VKG4
	FAM114A2	NM_001317993.2		c.1280A>C	p.Glu427Ala	missense	Exon 13 of 15	NP_001304922.1	Q9NRY5
	FAM114A2	NM_001317994.2		c.1280A>C	p.Glu427Ala	missense	Exon 12 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.1280A>C	p.Glu427Ala	missense	Exon 12 of 14	ENSP00000341597.4	Q9NRY5
	FAM114A2	ENST00000520667.5	TSL:1	c.1280A>C	p.Glu427Ala	missense	Exon 13 of 15	ENSP00000430384.1	Q9NRY5
	FAM114A2	ENST00000522858.5	TSL:1	c.1280A>C	p.Glu427Ala	missense	Exon 12 of 14	ENSP00000430489.1	Q9NRY5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000200 AC: 5 AN: 250008 AF XY: 0.0000222

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000442

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000117 AC: 17 AN: 1451906 Hom.: 0 Cov.: 26 AF XY: 0.0000180 AC XY: 13 AN XY: 722944

African (AFR) AF: 0.00 AC: 0 AN: 33272

American (AMR) AF: 0.00 AC: 0 AN: 44568

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26048

East Asian (EAS) AF: 0.00 AC: 0 AN: 39630

South Asian (SAS) AF: 0.00 AC: 0 AN: 85618

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.0000154 AC: 17 AN: 1103590

Other (OTH) AF: 0.00 AC: 0 AN: 60054

GnomAD4 genome Cov.: 32

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.33
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-0.91	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		5.7
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Benign	0.24
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.015	D
Polyphen		0.99	D
Vest4		0.62
MVP		0.38
MPC		0.14
ClinPred		0.84	D
GERP RS		5.3
Varity_R		0.54
gMVP		0.59
Mutation Taster		=62/38	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: rs373121338; hg19: chr5-153377412;