12-6445196-CT-GC

Variant names:

• chr12-6445196-CT-GC
• NM_001242.5:c.101_102delCTinsGC
• CD27 p.Ala34Gly

Variant summary

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

The NM_001242.5(CD27):​c.101_102delCTinsGC​(p.Ala34Gly) 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A34V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD27 NM_001242.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.396
• Publications: 0 publications found

Genes affected

CD27 (HGNC:11922): (CD27 molecule) The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is required for generation and long-term maintenance of T cell immunity. It binds to ligand CD70, and plays a key role in regulating B-cell activation and immunoglobulin synthesis. This receptor transduces signals that lead to the activation of NF-kappaB and MAPK8/JNK. Adaptor proteins TRAF2 and TRAF5 have been shown to mediate the signaling process of this receptor. CD27-binding protein (SIVA), a proapoptotic protein, can bind to this receptor and is thought to play an important role in the apoptosis induced by this receptor. [provided by RefSeq, Jul 2008]

CD27-AS1 (HGNC:43896): (CD27 antisense RNA 1)

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242.5. 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
	CD27	NM_001242.5	MANE Select	c.101_102delCTinsGC	p.Ala34Gly	missense	N/A	NP_001233.2	P26842
	CD27	NM_001413263.1		c.101_102delCTinsGC	p.Ala34Gly	missense	N/A	NP_001400192.1
	CD27	NM_001413264.1		c.101_102delCTinsGC	p.Ala34Gly	missense	N/A	NP_001400193.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD27	ENST00000266557.4	TSL:1 MANE Select	c.101_102delCTinsGC	p.Ala34Gly	missense	N/A	ENSP00000266557.3	P26842
	CD27-AS1	ENST00000399492.6	TSL:1	n.485-1480_485-1479delAGinsGC		intron	N/A
	CD27-AS1	ENST00000417058.6	TSL:1	n.814-1480_814-1479delAGinsGC		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.40

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: chr12-6554362;