2-238320719-G-C

Variant names:

• chr2-238320719-G-C
• rs1442403482
• NM_015650.4:c.57G>C

Variant summary

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

The NM_015650.4(TRAF3IP1):​c.57G>C​(p.Arg19Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R19M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TRAF3IP1 NM_015650.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99
• Publications: 0 publications found

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]

TRAF3IP1 Gene-Disease associations (from GenCC):

• Senior-Loken syndrome 9

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• Senior-Loken syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• short rib-polydactyly syndrome, Majewski type

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

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=0.10389361).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAF3IP1	NM_015650.4	c.57G>C	p.Arg19Ser	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.57G>C	p.Arg19Ser	missense_variant	Exon 1 of 17	1	NM_015650.4	ENSP00000362424.4
TRAF3IP1	ENST00000391993.7	c.57G>C	p.Arg19Ser	missense_variant	Exon 1 of 15	1		ENSP00000375851.3
TRAF3IP1	ENST00000409739.2	n.57G>C		non_coding_transcript_exon_variant	Exon 1 of 5	3		ENSP00000386648.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	.;T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.092
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.074	D
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.85	L;L
PhyloP100		2.0
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.039
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		0.32	B;B
Vest4		0.24
MutPred		0.32		Loss of MoRF binding (P = 0.0343);Loss of MoRF binding (P = 0.0343);
MVP		0.27
MPC		0.25
ClinPred		0.93	D
GERP RS		3.4
PromoterAI		-0.19	Neutral
Varity_R		0.78
gMVP		0.47
Mutation Taster		=50/50

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: rs1442403482; hg19: chr2-239229360;