17-20204747-A-G

Variant names:

• chr17-20204747-A-G
• NM_001243439.2:c.698A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001243439.2(SPECC1):​c.698A>G​(p.Asn233Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPECC1 NM_001243439.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.89
• Publications: 0 publications found

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]

ENSG00000263494 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001243439.2. 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
	SPECC1	NM_001243439.2	MANE Select	c.698A>G	p.Asn233Ser	missense	Exon 4 of 15	NP_001230368.1	Q5M775-1
	SPECC1	NM_001033553.3		c.698A>G	p.Asn233Ser	missense	Exon 4 of 15	NP_001028725.1	Q5M775-1
	SPECC1	NM_001386083.2		c.698A>G	p.Asn233Ser	missense	Exon 6 of 17	NP_001373012.2	Q5M775-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPECC1	ENST00000395527.9	TSL:2 MANE Select	c.698A>G	p.Asn233Ser	missense	Exon 4 of 15	ENSP00000378898.4	Q5M775-1
	SPECC1	ENST00000261503.9	TSL:1	c.698A>G	p.Asn233Ser	missense	Exon 4 of 15	ENSP00000261503.5	Q5M775-1
	SPECC1	ENST00000395530.6	TSL:1	c.455A>G	p.Asn152Ser	missense	Exon 2 of 13	ENSP00000378901.2	Q5M775-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 70

GnomAD4 genome Cov.: 32

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	Uncertain	0.38
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.097	T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Uncertain	0.18	D
MutationAssessor	Uncertain	2.6	M
PhyloP100		6.9
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.12
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.68
MutPred		0.28		Gain of phosphorylation at N233 (P = 0.0385)
MVP		0.81
MPC		0.24
ClinPred		0.94	D
GERP RS		4.2
Varity_R		0.18
gMVP		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

Other links and lift over

hg19: chr17-20108060;