17-7557197-G-T

Variant names:

• chr17-7557197-G-T
• rs143039184
• NM_003809.3:c.597G>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_003809.3(TNFSF12):​c.597G>T​(p.Ala199Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,459,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. A199A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: TNFSF12 NM_003809.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.26
• Publications: 0 publications found

Genes affected

TNFSF12 (HGNC:11927): (TNF superfamily member 12) The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This protein is a ligand for the FN14/TWEAKR receptor. This cytokine has overlapping signaling functions with TNF, but displays a much wider tissue distribution. This cytokine, which exists in both membrane-bound and secreted forms, can induce apoptosis via multiple pathways of cell death in a cell type-specific manner. This cytokine is also found to promote proliferation and migration of endothelial cells, and thus acts as a regulator of angiogenesis. Alternative splicing results in multiple transcript variants. Some transcripts skip the last exon of this gene and continue into the second exon of the neighboring TNFSF13 gene; such read-through transcripts are contained in GeneID 407977, TNFSF12-TNFSF13. [provided by RefSeq, Oct 2010]

TNFSF12-TNFSF13 (HGNC:33537): (TNFSF12-TNFSF13 readthrough) This gene encodes a member of the tumor necrosis factor superfamily. It encodes a hybrid protein composed of the cytoplasmic and transmembrane domains of family member 12 fused to the C-terminal domain of family member 13. The hybrid protein is membrane anchored and presents the receptor-binding domain of family member 13 at the cell surface. It stimulates cycling in T- and B-lymphoma cell lines. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 17-7557197-G-T is Benign according to our data. Variant chr17-7557197-G-T is described in CliVar as Likely_benign. Clinvar id is 3622478.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-7557197-G-T is described in CliVar as Likely_benign. Clinvar id is 3622478.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-7557197-G-T is described in CliVar as Likely_benign. Clinvar id is 3622478.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-7557197-G-T is described in CliVar as Likely_benign. Clinvar id is 3622478.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-7557197-G-T is described in CliVar as Likely_benign. Clinvar id is 3622478.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-7557197-G-T is described in CliVar as Likely_benign. Clinvar id is 3622478.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-7557197-G-T is described in CliVar as Likely_benign. Clinvar id is 3622478.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.26 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFSF12	NM_003809.3	c.597G>T	p.Ala199Ala	synonymous_variant	Exon 7 of 7	ENST00000293825.11	NP_003800.1
TNFSF12	NR_037146.2	n.932G>T		non_coding_transcript_exon_variant	Exon 8 of 8
TNFSF12-TNFSF13	NM_172089.4	c.498+295G>T		intron_variant	Intron 6 of 10		NP_742086.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFSF12	ENST00000293825.11	c.597G>T	p.Ala199Ala	synonymous_variant	Exon 7 of 7	1	NM_003809.3	ENSP00000293825.6
TNFSF12-TNFSF13	ENST00000293826.4	c.498+295G>T		intron_variant	Intron 6 of 10	1		ENSP00000293826.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00 AC: 0 AN: 250888 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000137 AC: 20 AN: 1459810 Hom.: 0 Cov.: 49 AF XY: 0.00000964 AC XY: 7 AN XY: 726276

African (AFR) AF: 0.00 AC: 0 AN: 33440

American (AMR) AF: 0.0000224 AC: 1 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53062

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5758

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1110594

Other (OTH) AF: 0.00 AC: 0 AN: 60330

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Common variable immunodeficiency Benign:1

May 25, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.096
DANN	Benign	0.71
PhyloP100		-2.3

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: rs143039184; hg19: chr17-7460514;