1-2559867-GCC-CCG

Variant names:

• chr1-2559867-GCC-CCG
• NM_003820.4:c.349_351delGCCinsCCG
• TNFRSF14 p.Ala117Pro

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_003820.4(TNFRSF14):​c.349_351delGCCinsCCG​(p.Ala117Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A117T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TNFRSF14 NM_003820.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.107
• Publications: 0 publications found

Genes affected

TNFRSF14 (HGNC:11912): (TNF receptor superfamily member 14) This gene encodes a member of the TNF (tumor necrosis factor) receptor superfamily. The encoded protein functions in signal transduction pathways that activate inflammatory and inhibitory T-cell immune response. It binds herpes simplex virus (HSV) viral envelope glycoprotein D (gD), mediating its entry into cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003820.4. 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
	TNFRSF14	NM_003820.4	MANE Select	c.349_351delGCCinsCCG	p.Ala117Pro	missense	N/A	NP_003811.2
	TNFRSF14	NM_001297605.2		c.349_351delGCCinsCCG	p.Ala117Pro	missense	N/A	NP_001284534.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF14	ENST00000355716.5	TSL:1 MANE Select	c.349_351delGCCinsCCG	p.Ala117Pro	missense	N/A	ENSP00000347948.4	Q92956-1
	TNFRSF14	ENST00000475523.5	TSL:1	n.586_588delGCCinsCCG		non_coding_transcript_exon	Exon 2 of 6
	TNFRSF14	ENST00000860787.1		c.613_615delGCCinsCCG	p.Ala205Pro	missense	N/A	ENSP00000530846.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.11

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-2491306;