rs3745727

Variant names:

• chr19-48603555-C-A
• NM_017708.4:c.1115G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-48603555-C-A
• chr19-48603555-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017708.4(FAM83E):​c.1115G>T​(p.Arg372Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000709 in 1,410,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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. R372H) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: FAM83E NM_017708.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.373

Genes affected

FAM83E (HGNC:25972): (family with sequence similarity 83 member E) Enables protein kinase binding activity. Predicted to be involved in signal transduction. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.111037195).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM83E	NM_017708.4	c.1115G>T	p.Arg372Leu	missense_variant	Exon 6 of 7	ENST00000263266.4	NP_060178.2
FAM83E	XM_024451561.2	c.1115G>T	p.Arg372Leu	missense_variant	Exon 6 of 7		XP_024307329.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM83E	ENST00000263266.4	c.1115G>T	p.Arg372Leu	missense_variant	Exon 6 of 7	1	NM_017708.4	ENSP00000263266.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 7.09e-7 AC: 1 AN: 1410862 Hom.: 0 Cov.: 30 AF XY: 0.00000142 AC XY: 1 AN XY: 702758

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: 9.13e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T
Eigen	Benign	0.098
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.053
Sift	Benign	0.14	T
Sift4G	Uncertain	0.011	D
Polyphen		0.67	P
Vest4		0.43
MutPred		0.23		Loss of MoRF binding (P = 0.0047);
MVP		0.20
MPC		0.55
ClinPred		0.94	D
GERP RS		4.5
Varity_R		0.14
gMVP		0.41

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: chr19-49106812;