rs2013441

chr17-20119786-G-A

Variant summary

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

The NM_001243439.2(SPECC1):c.283+9224G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 151,994 control chromosomes in the GnomAD database, including 8,194 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 0.29 (8194 hom., cov: 33)
• Consequence: SPECC1 NM_001243439.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.216

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPECC1	NM_001243439.2	c.283+9224G>A		intron_variant		ENST00000395527.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPECC1	ENST00000395527.9	c.283+9224G>A		intron_variant		2	NM_001243439.2	A2

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44199 AN: 151876 Hom.: 8197 Cov.: 33

Gnomad AFR AF: 0.0820

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.0127

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.342

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

GnomAD4 genome AF: 0.291 AC: 44195 AN: 151994 Hom.: 8194 Cov.: 33 AF XY: 0.289 AC XY: 21452 AN XY: 74268

Gnomad4 AFR AF: 0.0820

Gnomad4 AMR AF: 0.356

Gnomad4 ASJ AF: 0.438

Gnomad4 EAS AF: 0.0129

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.375

Gnomad4 NFE AF: 0.406

Gnomad4 OTH AF: 0.338

Alfa AF: 0.393 Hom.: 15309

Bravo AF: 0.288

Asia WGS AF: 0.112 AC: 393 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.0
Dann	Benign	0.62

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: rs2013441; hg19: chr17-20023099;