chr17-20110560-C-G

Variant names:

• chr17-20110560-C-G
• NM_001243439.2:c.281C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001243439.2(SPECC1):​c.281C>G​(p.Thr94Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPECC1 NM_001243439.2 missense, splice_region
• Scores: Splicing: ADA: 0.07861
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.53
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2857259).

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.281C>G	p.Thr94Arg	missense splice_region	Exon 3 of 15	NP_001230368.1	Q5M775-1
	SPECC1	NM_001033553.3		c.281C>G	p.Thr94Arg	missense splice_region	Exon 3 of 15	NP_001028725.1	Q5M775-1
	SPECC1	NM_001386083.2		c.281C>G	p.Thr94Arg	missense splice_region	Exon 5 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.281C>G	p.Thr94Arg	missense splice_region	Exon 3 of 15	ENSP00000378898.4	Q5M775-1
	SPECC1	ENST00000261503.9	TSL:1	c.281C>G	p.Thr94Arg	missense splice_region	Exon 3 of 15	ENSP00000261503.5	Q5M775-1
	SPECC1	ENST00000395529.7	TSL:1	c.281C>G	p.Thr94Arg	missense splice_region	Exon 3 of 8	ENSP00000378900.3	Q5M775-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	Benign	0.14
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.037	T
Eigen	Benign	0.068
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	1.2	L
PhyloP100		3.5
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.11
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.10	T
Polyphen		0.024	B
Vest4		0.29
MutPred		0.26		Gain of methylation at T94 (P = 0.0071)
MVP		0.66
MPC		0.12
ClinPred		0.50	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.079
dbscSNV1_RF	Benign	0.22
SpliceAI score (max)		0.010		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: chr17-20013873;