17-20066084-A-G

Position:

• chr17-20066084-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001243439.2(SPECC1):​c.-21-30547A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.939 in 152,254 control chromosomes in the GnomAD database, including 67,197 homozygotes. 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: 𝑓 0.94 (67197 hom., cov: 31)
• Consequence: SPECC1 NM_001243439.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112

Genes affected

SPECC1 (HGNC:30615): (sperm antigen with calponin homology and coiled-coil domains 1) The protein encoded by this gene belongs to the cytospin-A family. It is localized in the nucleus, and highly expressed in testis and some cancer cell lines. A chromosomal translocation involving this gene and platelet-derived growth factor receptor, beta gene (PDGFRB) may be a cause of juvenile myelomonocytic leukemia. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.979 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPECC1	NM_001243439.2	c.-21-30547A>G		intron_variant		ENST00000395527.9	NP_001230368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPECC1	ENST00000395527.9	c.-21-30547A>G		intron_variant		2	NM_001243439.2	ENSP00000378898	A2

Frequencies

GnomAD3 genomes AF: 0.939 AC: 142841 AN: 152136 Hom.: 67157 Cov.: 31

Gnomad AFR AF: 0.987

Gnomad AMI AF: 0.934

Gnomad AMR AF: 0.896

Gnomad ASJ AF: 0.856

Gnomad EAS AF: 0.959

Gnomad SAS AF: 0.882

Gnomad FIN AF: 0.908

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.931

Gnomad OTH AF: 0.929

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.939 AC: 142938 AN: 152254 Hom.: 67197 Cov.: 31 AF XY: 0.936 AC XY: 69635 AN XY: 74428

Gnomad4 AFR AF: 0.987

Gnomad4 AMR AF: 0.895

Gnomad4 ASJ AF: 0.856

Gnomad4 EAS AF: 0.960

Gnomad4 SAS AF: 0.881

Gnomad4 FIN AF: 0.908

Gnomad4 NFE AF: 0.931

Gnomad4 OTH AF: 0.923

Alfa AF: 0.928 Hom.: 36881

Bravo AF: 0.943

Asia WGS AF: 0.908 AC: 3161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.4
DANN	Benign	0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs7209752; hg19: chr17-19969397;