19-6586091-G-A

Variant names:

• chr19-6586091-G-A
• NM_001252.5:c.511C>T

Variant summary

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

The NM_001252.5(CD70):​c.511C>T​(p.Leu171Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CD70 NM_001252.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.69

Genes affected

CD70 (HGNC:11937): (CD70 molecule) The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This cytokine is a ligand for TNFRSF27/CD27. It is a surface antigen on activated, but not on resting, T and B lymphocytes. It induces proliferation of costimulated T cells, enhances the generation of cytolytic T cells, and contributes to T cell activation. This cytokine is also reported to play a role in regulating B-cell activation, cytotoxic function of natural killer cells, and immunoglobulin sythesis. [provided by RefSeq, Jul 2008]

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
CD70	NM_001252.5	c.511C>T	p.Leu171Phe	missense_variant	Exon 3 of 3	ENST00000245903.4	NP_001243.1
CD70	NM_001330332.2	c.448+63C>T		intron_variant	Intron 3 of 3		NP_001317261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD70	ENST00000245903.4	c.511C>T	p.Leu171Phe	missense_variant	Exon 3 of 3	1	NM_001252.5	ENSP00000245903.2
CD70	ENST00000423145.7	c.448+63C>T		intron_variant	Intron 3 of 3	2		ENSP00000395294.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Sep 16, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.511C>T (p.L171F) alteration is located in exon 3 (coding exon 3) of the CD70 gene. This alteration results from a C to T substitution at nucleotide position 511, causing the leucine (L) at amino acid position 171 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.89	D
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.75	T
M_CAP	Pathogenic	0.33	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Uncertain	0.23	D
MutationAssessor	Benign	1.7	L
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.7	D
REVEL	Pathogenic	0.67
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.40
MutPred		0.58		Gain of loop (P = 0.2045);
MVP		0.96
MPC		1.5
ClinPred		0.99	D
GERP RS		3.4
Varity_R		0.58

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-6586102;