2-238320680-G-A

Variant names:

• chr2-238320680-G-A
• rs2106351680
• NM_015650.4:c.18G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_015650.4(TRAF3IP1):​c.18G>A​(p.Val6Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000127 in 1,258,412 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: not found (cov: 33)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: TRAF3IP1 NM_015650.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.32

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

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 2-238320680-G-A is Benign according to our data. Variant chr2-238320680-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1634440.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.32 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAF3IP1	NM_015650.4	c.18G>A	p.Val6Val	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.18G>A	p.Val6Val	synonymous_variant	Exon 1 of 17	1	NM_015650.4	ENSP00000362424.4
TRAF3IP1	ENST00000391993.7	c.18G>A	p.Val6Val	synonymous_variant	Exon 1 of 15	1		ENSP00000375851.3
TRAF3IP1	ENST00000409739.2	n.18G>A		non_coding_transcript_exon_variant	Exon 1 of 5	3		ENSP00000386648.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000127 AC: 16 AN: 1258412 Hom.: 0 Cov.: 30 AF XY: 0.0000145 AC XY: 9 AN XY: 620438

African (AFR) AF: 0.00 AC: 0 AN: 25392

American (AMR) AF: 0.00 AC: 0 AN: 24738

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20506

East Asian (EAS) AF: 0.00 AC: 0 AN: 24968

South Asian (SAS) AF: 0.00 AC: 0 AN: 66590

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43244

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4558

European-Non Finnish (NFE) AF: 0.0000160 AC: 16 AN: 999116

Other (OTH) AF: 0.00 AC: 0 AN: 49300

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 23, 2024

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	-0.54
CADD	Benign	16
DANN	Uncertain	0.98
PhyloP100		2.3
PromoterAI		0.035	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Other links and lift over

dbSNP: rs2106351680; hg19: chr2-239229321;