6-34541114-C-T

Variant names:

• chr6-34541114-C-T
• rs2233643
• NM_012391.3:c.504G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_012391.3(SPDEF):​c.504G>A​(p.Leu168Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L168L) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SPDEF NM_012391.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.11
• 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP7: Synonymous conserved (PhyloP=3.11 with no splicing effect.

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.504G>A	p.Leu168Leu	synonymous	Exon 3 of 6	NP_036523.1	O95238-1
	SPDEF	NM_001252294.2		c.504G>A	p.Leu168Leu	synonymous	Exon 3 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.504G>A	p.Leu168Leu	synonymous	Exon 3 of 6	ENSP00000363149.3	O95238-1
	SPDEF	ENST00000886645.1		c.504G>A	p.Leu168Leu	synonymous	Exon 3 of 6	ENSP00000556704.1
	SPDEF	ENST00000943125.1		c.585G>A	p.Leu195Leu	synonymous	Exon 4 of 7	ENSP00000613184.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 240870 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: 0.00000137 AC: 2 AN: 1458066 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 724974

African (AFR) AF: 0.0000299 AC: 1 AN: 33426

American (AMR) AF: 0.00 AC: 0 AN: 44304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26012

East Asian (EAS) AF: 0.00 AC: 0 AN: 39624

South Asian (SAS) AF: 0.00 AC: 0 AN: 85338

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52686

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5728

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110772

Other (OTH) AF: 0.00 AC: 0 AN: 60176

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	9.1
DANN	Benign	0.73
PhyloP100		3.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2233643; hg19: chr6-34508891;