NM_015650.4:c.-99delC

Variant names:

• chr2-238320563-GC-G
• rs368022925
• NM_015650.4:c.-99delC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_015650.4(TRAF3IP1):​c.-99delC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.082 in 980,564 control chromosomes in the GnomAD database, including 3,436 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.062 (395 hom., cov: 32)
  • Exomes 𝑓: 0.086 (3041 hom.)
• Consequence: TRAF3IP1 NM_015650.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.166
• 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):

• 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 -10 ACMG points.

• BP6: Variant 2-238320563-GC-G is Benign according to our data. Variant chr2-238320563-GC-G is described in ClinVar as Benign. ClinVar VariationId is 1281208.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.091 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.-99delC		5_prime_UTR	Exon 1 of 17	NP_056465.2
	TRAF3IP1	NM_001139490.1		c.-99delC		5_prime_UTR	Exon 1 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.-99delC		5_prime_UTR	Exon 1 of 17	ENSP00000362424.4	Q8TDR0-1
	TRAF3IP1	ENST00000391993.7	TSL:1	c.-99delC		5_prime_UTR	Exon 1 of 15	ENSP00000375851.3	Q8TDR0-2
	TRAF3IP1	ENST00000935943.1		c.-99delC		5_prime_UTR	Exon 1 of 16	ENSP00000606002.1

Frequencies

GnomAD3 genomes AF: 0.0620 AC: 9340 AN: 150644 Hom.: 396 Cov.: 32

Gnomad AFR AF: 0.0145

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0379

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0518

Gnomad FIN AF: 0.0920

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.0929

Gnomad OTH AF: 0.0551

GnomAD4 exome AF: 0.0857 AC: 71088 AN: 829816 Hom.: 3041 Cov.: 11 AF XY: 0.0865 AC XY: 33648 AN XY: 389146

African (AFR) AF: 0.00939 AC: 145 AN: 15438

American (AMR) AF: 0.0503 AC: 110 AN: 2188

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 893 AN: 6002

East Asian (EAS) AF: 0.000992 AC: 5 AN: 5038

South Asian (SAS) AF: 0.0578 AC: 972 AN: 16828

European-Finnish (FIN) AF: 0.162 AC: 1073 AN: 6604

Middle Eastern (MID) AF: 0.0838 AC: 146 AN: 1742

European-Non Finnish (NFE) AF: 0.0873 AC: 65265 AN: 747826

Other (OTH) AF: 0.0881 AC: 2479 AN: 28150

GnomAD4 genome AF: 0.0619 AC: 9332 AN: 150748 Hom.: 395 Cov.: 32 AF XY: 0.0597 AC XY: 4399 AN XY: 73658

African (AFR) AF: 0.0144 AC: 597 AN: 41368

American (AMR) AF: 0.0378 AC: 573 AN: 15154

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 460 AN: 3450

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5170

South Asian (SAS) AF: 0.0514 AC: 248 AN: 4826

European-Finnish (FIN) AF: 0.0920 AC: 925 AN: 10056

Middle Eastern (MID) AF: 0.120 AC: 35 AN: 292

European-Non Finnish (NFE) AF: 0.0929 AC: 6265 AN: 67432

Other (OTH) AF: 0.0540 AC: 113 AN: 2092

Alfa AF: 0.0444 Hom.: 62

Bravo AF: 0.0543

Asia WGS AF: 0.0290 AC: 95 AN: 3306

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.17
Mutation Taster		=300/0	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: rs368022925; hg19: chr2-239229204;