rs199701408

Variant names:

• chr19-48603504-C-G
• rs199701408
• NM_017708.4:c.1166G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-48603504-C-G
• chr19-48603504-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017708.4(FAM83E):​c.1166G>C​(p.Gly389Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000294 in 1,566,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000031 (0 hom.)
• Consequence: FAM83E NM_017708.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.685
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.076866895).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017708.4. 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
	FAM83E	NM_017708.4	MANE Select	c.1166G>C	p.Gly389Ala	missense	Exon 6 of 7	NP_060178.2	Q2M2I3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM83E	ENST00000263266.4	TSL:1 MANE Select	c.1166G>C	p.Gly389Ala	missense	Exon 6 of 7	ENSP00000263266.2	Q2M2I3
	FAM83E	ENST00000876133.1		c.1166G>C	p.Gly389Ala	missense	Exon 5 of 6	ENSP00000546192.1
	FAM83E	ENST00000876134.1		c.1166G>C	p.Gly389Ala	missense	Exon 5 of 6	ENSP00000546193.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152252 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000454 AC: 9 AN: 198162 AF XY: 0.00000898

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000995

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000649

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000311 AC: 44 AN: 1414428 Hom.: 0 Cov.: 30 AF XY: 0.0000255 AC XY: 18 AN XY: 704652

African (AFR) AF: 0.00 AC: 0 AN: 30040

American (AMR) AF: 0.0000976 AC: 4 AN: 40968

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25074

East Asian (EAS) AF: 0.00 AC: 0 AN: 34934

South Asian (SAS) AF: 0.00 AC: 0 AN: 84186

European-Finnish (FIN) AF: 0.0000264 AC: 1 AN: 37894

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5644

European-Non Finnish (NFE) AF: 0.0000356 AC: 39 AN: 1096926

Other (OTH) AF: 0.00 AC: 0 AN: 58762

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152252 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 74386

African (AFR) AF: 0.00 AC: 0 AN: 41478

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000378

ExAC AF: 0.0000252 AC: 3

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	0.11
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.69
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.039
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.049	D
Polyphen		0.73	P
Vest4		0.30
MutPred		0.19		Loss of stability (P = 0.0254)
MVP		0.11
MPC		0.57
ClinPred		0.088	T
GERP RS		2.6
Varity_R		0.098
gMVP		0.30
Mutation Taster		=97/3	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: rs199701408; hg19: chr19-49106761; COSMIC: COSV104372502; COSMIC: COSV104372502;