rs11551509

Variant names:

• chr6-34537856-C-A
• rs11551509
• NM_012391.3:c.*418G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012391.3(SPDEF):​c.*418G>T variant causes a 3 prime UTR 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPDEF NM_012391.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26
• Publications: 1 publications found

Genes affected

SPDEF (HGNC:17257): (SAM pointed domain containing ETS transcription factor) The protein encoded by this gene belongs to the ETS family of transcription factors. It is highly expressed in the prostate epithelial cells, and functions as an androgen-independent transactivator of prostate-specific antigen (PSA) promoter. Higher expression of this protein has also been reported in brain, breast, lung and ovarian tumors, compared to the corresponding normal tissues, and it shows better tumor-association than other cancer-associated molecules, making it a more suitable target for developing specific cancer therapies. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012391.3. 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
	SPDEF	NM_012391.3	MANE Select	c.*418G>T		3_prime_UTR	Exon 6 of 6	NP_036523.1	O95238-1
	SPDEF	NM_001252294.2		c.*418G>T		3_prime_UTR	Exon 5 of 5	NP_001239223.1	O95238-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPDEF	ENST00000374037.8	TSL:1 MANE Select	c.*418G>T		3_prime_UTR	Exon 6 of 6	ENSP00000363149.3	O95238-1
	SPDEF	ENST00000886645.1		c.*418G>T		3_prime_UTR	Exon 6 of 6	ENSP00000556704.1
	SPDEF	ENST00000943125.1		c.*418G>T		3_prime_UTR	Exon 7 of 7	ENSP00000613184.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 16818 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 8770

African (AFR) AF: 0.00 AC: 0 AN: 744

American (AMR) AF: 0.00 AC: 0 AN: 2124

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 392

East Asian (EAS) AF: 0.00 AC: 0 AN: 1080

South Asian (SAS) AF: 0.00 AC: 0 AN: 1100

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 56

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 10024

Other (OTH) AF: 0.00 AC: 0 AN: 928

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.6
DANN	Benign	0.70
PhyloP100		1.3

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: rs11551509; hg19: chr6-34505633;