rs1592554584

Variant names:

• chr12-53382904-C-G
• rs1592554584
• NM_138473.3:c.957C>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_138473.3(SP1):​c.957C>G​(p.Ser319Ser) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SP1 NM_138473.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.404
• Publications: 0 publications found

Genes affected

SP1 (HGNC:11205): (Sp1 transcription factor) The protein encoded by this gene is a zinc finger transcription factor that binds to GC-rich motifs of many promoters. The encoded protein is involved in many cellular processes, including cell differentiation, cell growth, apoptosis, immune responses, response to DNA damage, and chromatin remodeling. Post-translational modifications such as phosphorylation, acetylation, glycosylation, and proteolytic processing significantly affect the activity of this protein, which can be an activator or a repressor. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2014]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 12-53382904-C-G is Benign according to our data. Variant chr12-53382904-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 745328.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.404 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138473.3. 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
	SP1	NM_138473.3	MANE Select	c.957C>G	p.Ser319Ser	synonymous	Exon 3 of 6	NP_612482.2
	SP1	NM_003109.1		c.936C>G	p.Ser312Ser	synonymous	Exon 3 of 6	NP_003100.1	P08047-2
	SP1	NM_001251825.2		c.813C>G	p.Ser271Ser	synonymous	Exon 3 of 6	NP_001238754.1	P08047-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP1	ENST00000327443.9	TSL:1 MANE Select	c.957C>G	p.Ser319Ser	synonymous	Exon 3 of 6	ENSP00000329357.4	P08047-1
	SP1	ENST00000426431.2	TSL:1	c.936C>G	p.Ser312Ser	synonymous	Exon 3 of 6	ENSP00000404263.2	P08047-2
	SP1	ENST00000854917.1		c.271+686C>G		intron	N/A	ENSP00000524976.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	11
DANN	Benign	0.70
PhyloP100		0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs1592554584; hg19: chr12-53776688;