1-209780527-G-A

Variant names:

• chr1-209780527-G-A
• rs1180866483
• NM_025228.4:c.1370G>A

Variant summary

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

The NM_025228.4(TRAF3IP3):​c.1370G>A​(p.Gly457Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000187 in 1,604,432 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TRAF3IP3 NM_025228.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.85
• Publications: 0 publications found

Genes affected

TRAF3IP3 (HGNC:30766): (TRAF3 interacting protein 3) The gene encodes a protein that mediates cell growth by modulating the c-Jun N-terminal kinase signal transduction pathway. The encoded protein may also interact with a large multi-protein assembly containing the phosphatase 2A catalytic subunit. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

C1orf74 (HGNC:26319): (chromosome 1 open reading frame 74)

ENSG00000289700 (HGNC:):

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=0.18297324).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025228.4. 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
	TRAF3IP3	NM_025228.4	MANE Select	c.1370G>A	p.Gly457Asp	missense	Exon 15 of 17	NP_079504.2	Q9Y228-1
	C1orf74	NM_152485.4	MANE Select	c.*2298C>T		3_prime_UTR	Exon 2 of 2	NP_689698.1	Q96LT6
	TRAF3IP3	NM_001320143.2		c.1370G>A	p.Gly457Asp	missense	Exon 15 of 17	NP_001307072.1	Q9Y228-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF3IP3	ENST00000367025.8	TSL:1 MANE Select	c.1370G>A	p.Gly457Asp	missense	Exon 15 of 17	ENSP00000355992.3	Q9Y228-1
	TRAF3IP3	ENST00000367026.7	TSL:1	c.1310G>A	p.Gly437Asp	missense	Exon 15 of 17	ENSP00000355993.3	Q9Y228-2
	C1orf74	ENST00000294811.2	TSL:1 MANE Select	c.*2298C>T		3_prime_UTR	Exon 2 of 2	ENSP00000294811.1	Q96LT6

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152182 Hom.: 0 Cov.: 33

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

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1452250 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 722616

African (AFR) AF: 0.00 AC: 0 AN: 32924

American (AMR) AF: 0.00 AC: 0 AN: 43972

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25932

East Asian (EAS) AF: 0.00 AC: 0 AN: 39112

South Asian (SAS) AF: 0.00 AC: 0 AN: 85018

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53280

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4858

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107316

Other (OTH) AF: 0.00 AC: 0 AN: 59838

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152182 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74358

African (AFR) AF: 0.00 AC: 0 AN: 41428

American (AMR) AF: 0.00 AC: 0 AN: 15282

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: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

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	0.088
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0059	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.36	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.8
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.23
Sift	Benign	0.033	D
Sift4G	Benign	0.12	T
Polyphen		0.83	P
Vest4		0.30
MutPred		0.19		Loss of methylation at K460 (P = 0.0693)
MVP		0.82
MPC		0.25
ClinPred		0.46	T
GERP RS		5.2
Varity_R		0.084
gMVP		0.051
Mutation Taster		=81/19	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: rs1180866483; hg19: chr1-209953872;