rs373121338

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr5-153997852-T-C
• chr5-153997852-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018691.4(FAM114A2):​c.1280A>G​(p.Glu427Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000062 in 1,451,906 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. E427A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: FAM114A2 NM_018691.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.73

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM114A2	NM_018691.4	c.1280A>G	p.Glu427Gly	missense_variant	Exon 12 of 14	ENST00000351797.9	NP_061161.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM114A2	ENST00000351797.9	c.1280A>G	p.Glu427Gly	missense_variant	Exon 12 of 14	1	NM_018691.4	ENSP00000341597.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000620 AC: 9 AN: 1451906 Hom.: 0 Cov.: 26 AF XY: 0.00000277 AC XY: 2 AN XY: 722944

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000634

Gnomad4 OTH exome AF: 0.0000333

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000370 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.017	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.32	T;T;T;T
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.92	.;.;D;D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.61	D;D;D;D
MetaSVM	Benign	-0.81	T
MutationAssessor	Pathogenic	2.9	M;M;M;.
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-5.9	D;D;D;D
REVEL	Benign	0.27
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Uncertain	0.0080	D;D;D;D
Polyphen		0.99	D;D;D;D
Vest4		0.65
MutPred		0.46		Loss of stability (P = 0.0367);Loss of stability (P = 0.0367);Loss of stability (P = 0.0367);.;
MVP		0.45
MPC		0.14
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.59
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs373121338; hg19: chr5-153377412;