3-172523280-G-A

Variant names:

• chr3-172523280-G-A
• rs41308132
• NM_003810.4:c.105C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_003810.4(TNFSF10):​c.105C>T​(p.Tyr35Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00478 in 1,613,910 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0030 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0050 (21 hom.)
• Consequence: TNFSF10 NM_003810.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.321
• Publications: 5 publications found

Genes affected

TNFSF10 (HGNC:11925): (TNF superfamily member 10) The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This protein preferentially induces apoptosis in transformed and tumor cells, but does not appear to kill normal cells although it is expressed at a significant level in most normal tissues. This protein binds to several members of TNF receptor superfamily including TNFRSF10A/TRAILR1, TNFRSF10B/TRAILR2, TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4, and possibly also to TNFRSF11B/OPG. The activity of this protein may be modulated by binding to the decoy receptors TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4, and TNFRSF11B/OPG that cannot induce apoptosis. The binding of this protein to its receptors has been shown to trigger the activation of MAPK8/JNK, caspase 8, and caspase 3. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 3-172523280-G-A is Benign according to our data. Variant chr3-172523280-G-A is described in ClinVar as Benign. ClinVar VariationId is 769617.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.321 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 21 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003810.4. 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
	TNFSF10	NM_003810.4	MANE Select	c.105C>T	p.Tyr35Tyr	synonymous	Exon 1 of 5	NP_003801.1	Q6IBA9
	TNFSF10	NM_001190942.2		c.105C>T	p.Tyr35Tyr	synonymous	Exon 1 of 3	NP_001177871.1	P50591-2
	TNFSF10	NM_001190943.2		c.105C>T	p.Tyr35Tyr	synonymous	Exon 1 of 2	NP_001177872.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF10	ENST00000241261.7	TSL:1 MANE Select	c.105C>T	p.Tyr35Tyr	synonymous	Exon 1 of 5	ENSP00000241261.2	P50591-1
	TNFSF10	ENST00000420541.6	TSL:1	c.105C>T	p.Tyr35Tyr	synonymous	Exon 1 of 3	ENSP00000389931.2	P50591-2
	TNFSF10	ENST00000466777.1	TSL:1	n.188C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.00304 AC: 463 AN: 152230 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.000753

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00520

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00324 AC: 813 AN: 251006 AF XY: 0.00311

Gnomad AFR exome AF: 0.000923

Gnomad AMR exome AF: 0.00257

Gnomad ASJ exome AF: 0.00189

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000693

Gnomad NFE exome AF: 0.00570

Gnomad OTH exome AF: 0.00327

GnomAD4 exome AF: 0.00497 AC: 7259 AN: 1461562 Hom.: 21 Cov.: 31 AF XY: 0.00483 AC XY: 3513 AN XY: 727122

African (AFR) AF: 0.000986 AC: 33 AN: 33466

American (AMR) AF: 0.00277 AC: 124 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00168 AC: 44 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.000383 AC: 33 AN: 86248

European-Finnish (FIN) AF: 0.00109 AC: 58 AN: 53404

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5764

European-Non Finnish (NFE) AF: 0.00599 AC: 6664 AN: 1111762

Other (OTH) AF: 0.00489 AC: 295 AN: 60378

GnomAD4 genome AF: 0.00304 AC: 463 AN: 152348 Hom.: 1 Cov.: 33 AF XY: 0.00286 AC XY: 213 AN XY: 74500

African (AFR) AF: 0.00108 AC: 45 AN: 41586

American (AMR) AF: 0.00262 AC: 40 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4830

European-Finnish (FIN) AF: 0.000753 AC: 8 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00520 AC: 354 AN: 68038

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.00444 Hom.: 2

Bravo AF: 0.00351

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00518

EpiControl AF: 0.00600

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.7
DANN	Benign	0.74
PhyloP100		0.32
PromoterAI		-0.030	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs41308132; hg19: chr3-172241070; COSMIC: COSV53843341; COSMIC: COSV53843341;