6-34544029-T-C

Variant names:

• chr6-34544029-T-C
• rs151017071
• NM_012391.3:c.427A>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_012391.3(SPDEF):​c.427A>G​(p.Ile143Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000309 in 1,610,604 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00033 (0 hom.)
• Consequence: SPDEF NM_012391.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.97
• Publications: 2 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.33973306).

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.427A>G	p.Ile143Val	missense	Exon 2 of 6	NP_036523.1	O95238-1
	SPDEF	NM_001252294.2		c.427A>G	p.Ile143Val	missense	Exon 2 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.427A>G	p.Ile143Val	missense	Exon 2 of 6	ENSP00000363149.3	O95238-1
	SPDEF	ENST00000886645.1		c.427A>G	p.Ile143Val	missense	Exon 2 of 6	ENSP00000556704.1
	SPDEF	ENST00000943125.1		c.427A>G	p.Ile143Val	missense	Exon 2 of 7	ENSP00000613184.1

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152206 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000222 AC: 55 AN: 247254 AF XY: 0.000224

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.000210

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000376

Gnomad OTH exome AF: 0.000663

GnomAD4 exome AF: 0.000325 AC: 474 AN: 1458398 Hom.: 0 Cov.: 31 AF XY: 0.000303 AC XY: 220 AN XY: 725526

African (AFR) AF: 0.00 AC: 0 AN: 33302

American (AMR) AF: 0.000207 AC: 9 AN: 43532

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25962

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.00 AC: 0 AN: 85750

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 0.000405 AC: 450 AN: 1110864

Other (OTH) AF: 0.000216 AC: 13 AN: 60240

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152206 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74358

African (AFR) AF: 0.0000724 AC: 3 AN: 41462

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000380 Hom.: 2

Bravo AF: 0.000166

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.000264 AC: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000416

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.36
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.098	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		8.0
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.24
Sift	Benign	0.13	T
Sift4G	Uncertain	0.023	D
Polyphen		0.94	P
Vest4		0.62
MVP		0.37
MPC		0.79
ClinPred		0.083	T
GERP RS		5.1
Varity_R		0.12
gMVP		0.26
Mutation Taster		=78/22	polymorphism

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: rs151017071; hg19: chr6-34511806;