19-48603658-C-A

Variant names:

• chr19-48603658-C-A
• rs780828161
• NM_017708.4:c.1012G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_017708.4(FAM83E):​c.1012G>T​(p.Ala338Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000114 in 1,311,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. A338P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: FAM83E NM_017708.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0170
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07931414).

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.1012G>T	p.Ala338Ser	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.1012G>T	p.Ala338Ser	missense	Exon 6 of 7	ENSP00000263266.2	Q2M2I3
	FAM83E	ENST00000876133.1		c.1012G>T	p.Ala338Ser	missense	Exon 5 of 6	ENSP00000546192.1
	FAM83E	ENST00000876134.1		c.1012G>T	p.Ala338Ser	missense	Exon 5 of 6	ENSP00000546193.1

Frequencies

GnomAD3 genomes AF: 0.00000660 AC: 1 AN: 151432 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: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000121 AC: 14 AN: 1159866 Hom.: 0 Cov.: 29 AF XY: 0.0000107 AC XY: 6 AN XY: 559166

African (AFR) AF: 0.00 AC: 0 AN: 23862

American (AMR) AF: 0.00 AC: 0 AN: 11950

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15164

East Asian (EAS) AF: 0.00 AC: 0 AN: 27998

South Asian (SAS) AF: 0.000298 AC: 11 AN: 36936

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33888

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3260

European-Non Finnish (NFE) AF: 0.00000312 AC: 3 AN: 960448

Other (OTH) AF: 0.00 AC: 0 AN: 46360

GnomAD4 genome AF: 0.00000660 AC: 1 AN: 151432 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 73982

African (AFR) AF: 0.00 AC: 0 AN: 41380

American (AMR) AF: 0.00 AC: 0 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10222

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67842

Other (OTH) AF: 0.00 AC: 0 AN: 2078

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		-0.017
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.036
Sift	Benign	0.053	T
Sift4G	Uncertain	0.025	D
Polyphen		0.29	B
Vest4		0.17
MutPred		0.25		Gain of glycosylation at A338 (P = 0.0181)
MVP		0.11
MPC		0.39
ClinPred		0.26	T
GERP RS		2.8
Varity_R		0.056
gMVP		0.32
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: rs780828161; hg19: chr19-49106915;