chr12-6328935-A-AAAAACAAAAC

Variant names:

• chr12-6328935-A-AAAAACAAAAC
• rs554776242
• NM_001065.4:c.*367_*376dupGTTTTGTTTT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001065.4(TNFRSF1A):​c.*367_*376dupGTTTTGTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TNFRSF1A NM_001065.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.589

Genes affected

TNFRSF1A (HGNC:11916): (TNF receptor superfamily member 1A) This gene encodes a member of the TNF receptor superfamily of proteins. The encoded receptor is found in membrane-bound and soluble forms that interact with membrane-bound and soluble forms, respectively, of its ligand, tumor necrosis factor alpha. Binding of membrane-bound tumor necrosis factor alpha to the membrane-bound receptor induces receptor trimerization and activation, which plays a role in cell survival, apoptosis, and inflammation. Proteolytic processing of the encoded receptor results in release of the soluble form of the receptor, which can interact with free tumor necrosis factor alpha to inhibit inflammation. Mutations in this gene underlie tumor necrosis factor receptor-associated periodic syndrome (TRAPS), characterized by fever, abdominal pain and other features. Mutations in this gene may also be associated with multiple sclerosis in human patients. [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF1A	NM_001065.4	c.*367_*376dupGTTTTGTTTT		3_prime_UTR_variant	Exon 10 of 10	ENST00000162749.7	NP_001056.1
TNFRSF1A	NM_001346091.2	c.*367_*376dupGTTTTGTTTT		3_prime_UTR_variant	Exon 9 of 9		NP_001333020.1
TNFRSF1A	NM_001346092.2	c.*367_*376dupGTTTTGTTTT		3_prime_UTR_variant	Exon 11 of 11		NP_001333021.1
TNFRSF1A	NR_144351.2	n.1923_1932dupGTTTTGTTTT		non_coding_transcript_exon_variant	Exon 9 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF1A	ENST00000162749	c.*367_*376dupGTTTTGTTTT		3_prime_UTR_variant	Exon 10 of 10	1	NM_001065.4	ENSP00000162749.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs554776242; hg19: chr12-6438101;