NM_017708.4:c.1270C>A

Variant names:

• chr19-48601276-G-T
• rs537095726
• NM_017708.4:c.1270C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_017708.4(FAM83E):​c.1270C>A​(p.Arg424Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,436,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: FAM83E NM_017708.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.24
• Publications: 0 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP7: Synonymous conserved (PhyloP=3.24 with no splicing effect.

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.1270C>A	p.Arg424Arg	synonymous	Exon 7 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.1270C>A	p.Arg424Arg	synonymous	Exon 7 of 7	ENSP00000263266.2	Q2M2I3
	FAM83E	ENST00000876133.1		c.1270C>A	p.Arg424Arg	synonymous	Exon 6 of 6	ENSP00000546192.1
	FAM83E	ENST00000876134.1		c.1270C>A	p.Arg424Arg	synonymous	Exon 6 of 6	ENSP00000546193.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1436210 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 712426

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32914

American (AMR) AF: 0.00 AC: 0 AN: 40646

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25600

East Asian (EAS) AF: 0.0000262 AC: 1 AN: 38222

South Asian (SAS) AF: 0.00 AC: 0 AN: 83418

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51258

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5724

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1099126

Other (OTH) AF: 0.00 AC: 0 AN: 59302

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.7
DANN	Benign	0.75
PhyloP100		3.2

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: rs537095726; hg19: chr19-49104533;