12-53412871-C-T

Position:

• chr12-53412871-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138473.3(SP1):​c.*1631C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.049 in 152,524 control chromosomes in the GnomAD database, including 287 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 0.049 (287 hom., cov: 31)
  • Exomes 𝑓: 0.054 (0 hom.)
• Consequence: SP1 NM_138473.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.815

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.07 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SP1	NM_138473.3	c.*1631C>T		3_prime_UTR_variant	6/6	ENST00000327443.9	NP_612482.2
SP1	NM_003109.1	c.*1631C>T		3_prime_UTR_variant	6/6		NP_003100.1
SP1	NM_001251825.2	c.*1631C>T		3_prime_UTR_variant	6/6		NP_001238754.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SP1	ENST00000327443.9	c.*1631C>T		3_prime_UTR_variant	6/6	1	NM_138473.3	ENSP00000329357.4
SP1	ENST00000426431.2	c.*1631C>T		3_prime_UTR_variant	6/6	1		ENSP00000404263.2

Frequencies

GnomAD3 genomes AF: 0.0491 AC: 7454 AN: 151960 Hom.: 287 Cov.: 31

Gnomad AFR AF: 0.0110

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0444

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0284

Gnomad FIN AF: 0.0628

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0717

Gnomad OTH AF: 0.0633

GnomAD4 exome AF: 0.0538 AC: 24 AN: 446 Hom.: 0 Cov.: 0 AF XY: 0.0474 AC XY: 13 AN XY: 274

Gnomad4 FIN exome AF: 0.0561

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0490 AC: 7446 AN: 152078 Hom.: 287 Cov.: 31 AF XY: 0.0482 AC XY: 3582 AN XY: 74332

Gnomad4 AFR AF: 0.0110

Gnomad4 AMR AF: 0.0443

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0282

Gnomad4 FIN AF: 0.0628

Gnomad4 NFE AF: 0.0717

Gnomad4 OTH AF: 0.0627

Alfa AF: 0.0662 Hom.: 512

Bravo AF: 0.0467

Asia WGS AF: 0.0130 AC: 44 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	4.0
DANN	Benign	0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17695156; hg19: chr12-53806655;