rs754605781

Variant names:

• chr17-20204470-C-G
• rs754605781
• NM_001243439.2:c.421C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-20204470-C-G
• chr17-20204470-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001386080.1(SPECC1):​c.-252C>G variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SPECC1 NM_001386080.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.31
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21777984).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386080.1. 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.421C>G	p.Pro141Ala	missense	Exon 4 of 15	NP_001230368.1	Q5M775-1
	SPECC1	NM_001386080.1		c.-252C>G		5_prime_UTR_premature_start_codon_gain	Exon 5 of 16	NP_001373009.1
	SPECC1	NM_001033553.3		c.421C>G	p.Pro141Ala	missense	Exon 4 of 15	NP_001028725.1	Q5M775-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPECC1	ENST00000395527.9	TSL:2 MANE Select	c.421C>G	p.Pro141Ala	missense	Exon 4 of 15	ENSP00000378898.4	Q5M775-1
	SPECC1	ENST00000261503.9	TSL:1	c.421C>G	p.Pro141Ala	missense	Exon 4 of 15	ENSP00000261503.5	Q5M775-1
	SPECC1	ENST00000395530.6	TSL:1	c.178C>G	p.Pro60Ala	missense	Exon 2 of 13	ENSP00000378901.2	Q5M775-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461880 Hom.: 0 Cov.: 70 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112002

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	16
DANN	Benign	0.78
DEOGEN2	Benign	0.011	T
Eigen	Benign	0.016
Eigen_PC	Benign	0.023
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.6	L
PhyloP100		4.3
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.24	N
REVEL	Benign	0.13
Sift	Benign	0.22	T
Sift4G	Benign	0.26	T
Polyphen		0.033	B
Vest4		0.21
MutPred		0.11		Gain of MoRF binding (P = 0.0359)
MVP		0.60
MPC		0.15
ClinPred		0.55	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.089

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

dbSNP: rs754605781; hg19: chr17-20107783;