12-6445462-G-T

Variant names:

• chr12-6445462-G-T
• rs25680
• NM_001242.5:c.175G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001242.5(CD27):​c.175G>T​(p.Ala59Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. 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. A59T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CD27 NM_001242.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.872
• Publications: 52 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09372541).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD27	NM_001242.5	c.175G>T	p.Ala59Ser	missense_variant	Exon 2 of 6	ENST00000266557.4	NP_001233.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD27	ENST00000266557.4	c.175G>T	p.Ala59Ser	missense_variant	Exon 2 of 6	1	NM_001242.5	ENSP00000266557.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 16403

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.046	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	9.1
DANN	Benign	0.89
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.086	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-0.45	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.87
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.097
Sift	Benign	0.52	T
Sift4G	Benign	0.68	T
Vest4		0.12
ClinPred		0.071	T
GERP RS		2.7
Varity_R		0.095
gMVP		0.55
Mutation Taster		=98/2	polymorphism

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: rs25680; hg19: chr12-6554628;