rs1697476086

Variant names:

• chr2-238320670-C-A
• NM_015650.4:c.8C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-238320670-C-A
• chr2-238320670-C-G
• chr2-238320670-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015650.4(TRAF3IP1):​c.8C>A​(p.Ala3Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000403 in 1,241,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. A3G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000040 (0 hom.)
• Consequence: TRAF3IP1 NM_015650.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.395

Genes affected

TRAF3IP1 (HGNC:17861): (TRAF3 interacting protein 1) The protein encoded by this gene interacts with TNF receptor-associated factor 3, tethering it to cytoskeletal microtubules. The encoded protein is also an inhibitor of the innate type I IFN response. Defects in this gene are a cause of Senior-Loken syndrome 9. [provided by RefSeq, Mar 2017]

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=0.07493213).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAF3IP1	NM_015650.4	c.8C>A	p.Ala3Glu	missense_variant	Exon 1 of 17	ENST00000373327.5	NP_056465.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAF3IP1	ENST00000373327.5	c.8C>A	p.Ala3Glu	missense_variant	Exon 1 of 17	1	NM_015650.4	ENSP00000362424.4
TRAF3IP1	ENST00000391993.7	c.8C>A	p.Ala3Glu	missense_variant	Exon 1 of 15	1		ENSP00000375851.3
TRAF3IP1	ENST00000409739.2	n.8C>A		non_coding_transcript_exon_variant	Exon 1 of 5	3		ENSP00000386648.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000403 AC: 5 AN: 1241124 Hom.: 0 Cov.: 30 AF XY: 0.00000164 AC XY: 1 AN XY: 611382

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000506

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0057	.;T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.64	T;T
M_CAP	Benign	0.081	D
MetaRNN	Benign	0.075	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.075	N;N
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.13	N;N
REVEL	Benign	0.022
Sift	Benign	0.29	T;T
Sift4G	Benign	0.23	T;T
Polyphen		0.0010	B;B
Vest4		0.12
MutPred		0.36		Gain of helix (P = 0.0078);Gain of helix (P = 0.0078);
MVP		0.16
MPC		0.16
ClinPred		0.25	T
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.14
gMVP		0.42

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-239229311;