rs778074512

Variant names:

• chr19-48601278-G-A
• rs778074512
• NM_017708.4:c.1268C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-48601278-G-A
• chr19-48601278-G-C
• chr19-48601278-G-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.1268C>T​(p.Ser423Phe) 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. 14/21 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. S423Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FAM83E NM_017708.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.18

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=0.13172734).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM83E	NM_017708.4	c.1268C>T	p.Ser423Phe	missense_variant	Exon 7 of 7	ENST00000263266.4	NP_060178.2
FAM83E	XM_024451561.2	c.1268C>T	p.Ser423Phe	missense_variant	Exon 7 of 7		XP_024307329.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM83E	ENST00000263266.4	c.1268C>T	p.Ser423Phe	missense_variant	Exon 7 of 7	1	NM_017708.4	ENSP00000263266.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.068
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.032	D
Polyphen		0.32	B
Vest4		0.19
MutPred		0.17		Loss of glycosylation at S423 (P = 0.0249);
MVP		0.18
MPC		0.34
ClinPred		0.26	T
GERP RS		2.4
Varity_R		0.097
gMVP		0.11

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

LitVar

Other links and lift over

dbSNP: rs778074512; hg19: chr19-49104535;