12-53383387-A-G

Variant names:

• chr12-53383387-A-G
• rs3741651
• NM_138473.3:c.1440A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_138473.3(SP1):​c.1440A>G​(p.Gln480Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,614,024 control chromosomes in the GnomAD database, including 24,865 homozygotes. 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: 𝑓 0.18 (2647 hom., cov: 32)
  • Exomes 𝑓: 0.17 (22218 hom.)
• Consequence: SP1 NM_138473.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.22
• Publications: 25 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP7: Synonymous conserved (PhyloP=2.22 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP1	NM_138473.3	MANE Select	c.1440A>G	p.Gln480Gln	synonymous	Exon 3 of 6	NP_612482.2
	SP1	NM_003109.1		c.1419A>G	p.Gln473Gln	synonymous	Exon 3 of 6	NP_003100.1
	SP1	NM_001251825.2		c.1296A>G	p.Gln432Gln	synonymous	Exon 3 of 6	NP_001238754.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP1	ENST00000327443.9	TSL:1 MANE Select	c.1440A>G	p.Gln480Gln	synonymous	Exon 3 of 6	ENSP00000329357.4
	SP1	ENST00000426431.2	TSL:1	c.1419A>G	p.Gln473Gln	synonymous	Exon 3 of 6	ENSP00000404263.2

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27766 AN: 152040 Hom.: 2643 Cov.: 32

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.165

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.157

GnomAD2 exomes AF: 0.173 AC: 43625 AN: 251460 AF XY: 0.171

Gnomad AFR exome AF: 0.212

Gnomad AMR exome AF: 0.198

Gnomad ASJ exome AF: 0.141

Gnomad EAS exome AF: 0.193

Gnomad FIN exome AF: 0.157

Gnomad NFE exome AF: 0.170

Gnomad OTH exome AF: 0.157

GnomAD4 exome AF: 0.172 AC: 251761 AN: 1461866 Hom.: 22218 Cov.: 35 AF XY: 0.171 AC XY: 124190 AN XY: 727236

African (AFR) AF: 0.205 AC: 6873 AN: 33480

American (AMR) AF: 0.203 AC: 9078 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 3594 AN: 26136

East Asian (EAS) AF: 0.211 AC: 8382 AN: 39700

South Asian (SAS) AF: 0.152 AC: 13097 AN: 86258

European-Finnish (FIN) AF: 0.158 AC: 8418 AN: 53420

Middle Eastern (MID) AF: 0.0969 AC: 559 AN: 5768

European-Non Finnish (NFE) AF: 0.172 AC: 191686 AN: 1111988

Other (OTH) AF: 0.167 AC: 10074 AN: 60392

GnomAD4 genome AF: 0.183 AC: 27782 AN: 152158 Hom.: 2647 Cov.: 32 AF XY: 0.182 AC XY: 13501 AN XY: 74382

African (AFR) AF: 0.209 AC: 8697 AN: 41514

American (AMR) AF: 0.203 AC: 3093 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 408 AN: 3470

East Asian (EAS) AF: 0.198 AC: 1022 AN: 5174

South Asian (SAS) AF: 0.149 AC: 718 AN: 4820

European-Finnish (FIN) AF: 0.156 AC: 1657 AN: 10594

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11685 AN: 67996

Other (OTH) AF: 0.155 AC: 327 AN: 2114

Alfa AF: 0.174 Hom.: 1973

Bravo AF: 0.184

Asia WGS AF: 0.150 AC: 521 AN: 3478

EpiCase AF: 0.166

EpiControl AF: 0.162

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	12
DANN	Benign	0.91
PhyloP100		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	polymorphism (auto)

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: rs3741651; hg19: chr12-53777171; COSMIC: COSV59404162; COSMIC: COSV59404162;