NM_015650.4:c.90C>G

Variant names:

• chr2-238320752-C-G
• rs1183349435
• NM_015650.4:c.90C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_015650.4(TRAF3IP1):​c.90C>G​(p.Pro30Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000416 in 1,440,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: TRAF3IP1 NM_015650.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.417
• 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: 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=-0.46).
• BP6: Variant 2-238320752-C-G is Benign according to our data. Variant chr2-238320752-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1934652.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.417 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAF3IP1	NM_015650.4	c.90C>G	p.Pro30Pro	synonymous_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.90C>G	p.Pro30Pro	synonymous_variant	Exon 1 of 17	1	NM_015650.4	ENSP00000362424.4
TRAF3IP1	ENST00000391993.7	c.90C>G	p.Pro30Pro	synonymous_variant	Exon 1 of 15	1		ENSP00000375851.3
TRAF3IP1	ENST00000409739.2	n.90C>G		non_coding_transcript_exon_variant	Exon 1 of 5	3		ENSP00000386648.2

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151356 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 99066 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000233 AC: 3 AN: 1289302 Hom.: 0 Cov.: 33 AF XY: 0.00000472 AC XY: 3 AN XY: 636170

African (AFR) AF: 0.00 AC: 0 AN: 25908

American (AMR) AF: 0.000113 AC: 3 AN: 26444

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21440

East Asian (EAS) AF: 0.00 AC: 0 AN: 26272

South Asian (SAS) AF: 0.00 AC: 0 AN: 70876

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45118

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5140

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1016894

Other (OTH) AF: 0.00 AC: 0 AN: 51210

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151356 Hom.: 0 Cov.: 33 AF XY: 0.0000406 AC XY: 3 AN XY: 73918

African (AFR) AF: 0.00 AC: 0 AN: 41340

American (AMR) AF: 0.000197 AC: 3 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10326

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67734

Other (OTH) AF: 0.00 AC: 0 AN: 2072

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 19, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	13
DANN	Benign	0.87
PhyloP100		0.42
PromoterAI		0.086	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	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: rs1183349435; hg19: chr2-239229393;