17-20110560-C-G

Position:

• chr17-20110560-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 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. 16/23 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

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 Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPECC1	NM_001243439.2	c.281C>G	p.Thr94Arg	missense_variant, splice_region_variant	3/15	ENST00000395527.9	NP_001230368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPECC1	ENST00000395527.9	c.281C>G	p.Thr94Arg	missense_variant, splice_region_variant	3/15	2	NM_001243439.2	ENSP00000378898	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 02, 2021

The c.281C>G (p.T94R) alteration is located in exon 1 (coding exon 1) of the SPECC1 gene. This alteration results from a C to G substitution at nucleotide position 281, causing the threonine (T) at amino acid position 94 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;.;.;T;T
Eigen	Benign	0.068
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.70	.;T;T;T;T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.29	T;T;T;T;T;T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	1.2	L;.;.;L;L;.
MutationTaster	Benign	0.81	D;D;D
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.6	.;.;.;N;N;.
REVEL	Benign	0.11
Sift	Uncertain	0.0080	.;.;.;D;D;.
Sift4G	Benign	0.10	T;D;D;D;T;D
Polyphen		0.024	B;.;.;P;B;.
Vest4		0.29
MutPred		0.26		Gain of methylation at T94 (P = 0.0071);Gain of methylation at T94 (P = 0.0071);Gain of methylation at T94 (P = 0.0071);Gain of methylation at T94 (P = 0.0071);Gain of methylation at T94 (P = 0.0071);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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-20013873;