chr2-238329333-T-C

Variant names:

• chr2-238329333-T-C
• rs17854985
• NM_015650.4:c.906T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_015650.4(TRAF3IP1):​c.906T>C​(p.Pro302Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0588 in 1,357,820 control chromosomes in the GnomAD database, including 4,433 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P302P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.12 (1753 hom., cov: 32)
  • Exomes 𝑓: 0.052 (2680 hom.)
• Consequence: TRAF3IP1 NM_015650.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.68
• Publications: 5 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):

• ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Senior-Loken syndrome 9

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
• 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 2-238329333-T-C is Benign according to our data. Variant chr2-238329333-T-C is described in ClinVar as Benign. ClinVar VariationId is 1167551.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.68 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015650.4. 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
	TRAF3IP1	NM_015650.4	MANE Select	c.906T>C	p.Pro302Pro	synonymous	Exon 5 of 17	NP_056465.2
	TRAF3IP1	NM_001139490.1		c.906T>C	p.Pro302Pro	synonymous	Exon 5 of 15	NP_001132962.1	Q8TDR0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF3IP1	ENST00000373327.5	TSL:1 MANE Select	c.906T>C	p.Pro302Pro	synonymous	Exon 5 of 17	ENSP00000362424.4	Q8TDR0-1
	TRAF3IP1	ENST00000391993.7	TSL:1	c.906T>C	p.Pro302Pro	synonymous	Exon 5 of 15	ENSP00000375851.3	Q8TDR0-2
	TRAF3IP1	ENST00000935943.1		c.906T>C	p.Pro302Pro	synonymous	Exon 5 of 16	ENSP00000606002.1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17696 AN: 151986 Hom.: 1748 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0815

Gnomad ASJ AF: 0.0473

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0394

Gnomad OTH AF: 0.0980

GnomAD2 exomes AF: 0.0804 AC: 10662 AN: 132600 AF XY: 0.0752

Gnomad AFR exome AF: 0.263

Gnomad AMR exome AF: 0.0730

Gnomad ASJ exome AF: 0.0404

Gnomad EAS exome AF: 0.107

Gnomad FIN exome AF: 0.106

Gnomad NFE exome AF: 0.0401

Gnomad OTH exome AF: 0.0807

GnomAD4 exome AF: 0.0516 AC: 62170 AN: 1205716 Hom.: 2680 Cov.: 32 AF XY: 0.0515 AC XY: 29862 AN XY: 579336

African (AFR) AF: 0.281 AC: 7295 AN: 25966

American (AMR) AF: 0.0757 AC: 1566 AN: 20676

Ashkenazi Jewish (ASJ) AF: 0.0422 AC: 686 AN: 16252

East Asian (EAS) AF: 0.111 AC: 3634 AN: 32638

South Asian (SAS) AF: 0.0967 AC: 3332 AN: 34464

European-Finnish (FIN) AF: 0.101 AC: 4359 AN: 42964

Middle Eastern (MID) AF: 0.100 AC: 476 AN: 4754

European-Non Finnish (NFE) AF: 0.0384 AC: 37644 AN: 979310

Other (OTH) AF: 0.0653 AC: 3178 AN: 48692

GnomAD4 genome AF: 0.117 AC: 17728 AN: 152104 Hom.: 1753 Cov.: 32 AF XY: 0.119 AC XY: 8838 AN XY: 74378

African (AFR) AF: 0.268 AC: 11105 AN: 41446

American (AMR) AF: 0.0817 AC: 1248 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0473 AC: 164 AN: 3470

East Asian (EAS) AF: 0.102 AC: 529 AN: 5176

South Asian (SAS) AF: 0.113 AC: 545 AN: 4818

European-Finnish (FIN) AF: 0.114 AC: 1206 AN: 10596

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0394 AC: 2679 AN: 68000

Other (OTH) AF: 0.0970 AC: 205 AN: 2114

Alfa AF: 0.0453 Hom.: 116

Bravo AF: 0.120

Asia WGS AF: 0.0980 AC: 341 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	TRAF3IP1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.047
DANN	Benign	0.16
PhyloP100		-2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs17854985; hg19: chr2-239237974; COSMIC: COSV64852069;