5-272714-C-T

Variant names:

• chr5-272714-C-T
• rs145036962
• NM_013232.4:c.105C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001267558.2(PDCD6):​c.-106C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 1,574,744 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (2 hom., cov: 26)
  • Exomes 𝑓: 0.0010 (17 hom.)
• Consequence: PDCD6 NM_001267558.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.358
• Publications: 1 publications found

Genes affected

PDCD6 (HGNC:8765): (programmed cell death 6) This gene encodes a calcium-binding protein belonging to the penta-EF-hand protein family. Calcium binding is important for homodimerization and for conformational changes required for binding to other protein partners. This gene product participates in T cell receptor-, Fas-, and glucocorticoid-induced programmed cell death. In mice deficient for this gene product, however, apoptosis was not blocked suggesting this gene product is functionally redundant. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is also located on the short arm of chromosome 5. [provided by RefSeq, May 2012]

PDCD6-AHRR (HGNC:54724): (PDCD6-AHRR readthrough (NMD candidate)) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000286001 (HGNC:):

PDCD6-DT (HGNC:55580): (PDCD6 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 5-272714-C-T is Benign according to our data. Variant chr5-272714-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2655242.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001267558.2. 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
	PDCD6	NM_013232.4	MANE Select	c.105C>T	p.Val35Val	synonymous	Exon 2 of 6	NP_037364.1	O75340-1
	PDCD6	NM_001267558.2		c.-106C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 7	NP_001254487.1	A0A024QZ42
	PDCD6	NM_001267556.2		c.105C>T	p.Val35Val	synonymous	Exon 2 of 6	NP_001254485.1	O75340-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDCD6	ENST00000264933.9	TSL:1 MANE Select	c.105C>T	p.Val35Val	synonymous	Exon 2 of 6	ENSP00000264933.4	O75340-1
	PDCD6	ENST00000507528.5	TSL:1	c.105C>T	p.Val35Val	synonymous	Exon 2 of 6	ENSP00000423815.1	O75340-2
	PDCD6	ENST00000509581.5	TSL:1	c.105C>T	p.Val35Val	synonymous	Exon 2 of 3	ENSP00000422691.1	Q86W51

Frequencies

GnomAD3 genomes AF: 0.00131 AC: 189 AN: 143952 Hom.: 2 Cov.: 26

Gnomad AFR AF: 0.0000286

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000136

Gnomad ASJ AF: 0.000585

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00393

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00208

Gnomad OTH AF: 0.00101

GnomAD2 exomes AF: 0.00142 AC: 314 AN: 221640 AF XY: 0.00129

Gnomad AFR exome AF: 0.000268

Gnomad AMR exome AF: 0.0000717

Gnomad ASJ exome AF: 0.00222

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00251

Gnomad NFE exome AF: 0.00226

Gnomad OTH exome AF: 0.000937

GnomAD4 exome AF: 0.00103 AC: 1475 AN: 1430696 Hom.: 17 Cov.: 30 AF XY: 0.00106 AC XY: 754 AN XY: 708444

African (AFR) AF: 0.0000673 AC: 2 AN: 29710

American (AMR) AF: 0.0000483 AC: 2 AN: 41434

Ashkenazi Jewish (ASJ) AF: 0.00143 AC: 36 AN: 25188

East Asian (EAS) AF: 0.00 AC: 0 AN: 39220

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84692

European-Finnish (FIN) AF: 0.00300 AC: 159 AN: 52952

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5270

European-Non Finnish (NFE) AF: 0.00111 AC: 1215 AN: 1093640

Other (OTH) AF: 0.00102 AC: 60 AN: 58590

GnomAD4 genome AF: 0.00131 AC: 189 AN: 144048 Hom.: 2 Cov.: 26 AF XY: 0.00147 AC XY: 103 AN XY: 70272

African (AFR) AF: 0.0000285 AC: 1 AN: 35070

American (AMR) AF: 0.000136 AC: 2 AN: 14674

Ashkenazi Jewish (ASJ) AF: 0.000585 AC: 2 AN: 3416

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4716

European-Finnish (FIN) AF: 0.00393 AC: 41 AN: 10426

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.00208 AC: 140 AN: 67416

Other (OTH) AF: 0.000998 AC: 2 AN: 2004

Alfa AF: 0.00241 Hom.: 2

Bravo AF: 0.000718

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.0
DANN	Benign	0.77
PhyloP100		-0.36
PromoterAI		-0.029	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs145036962; hg19: chr5-272829;