NM_003111.5:c.2142A>C

Variant names:

• chr2-173910145-T-G
• rs7561583
• NM_003111.5:c.2142A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_003111.5(SP3):​c.2142A>C​(p.Thr714Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00185 in 1,613,902 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0095 (27 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (29 hom.)
• Consequence: SP3 NM_003111.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.87
• Publications: 0 publications found

Genes affected

SP3 (HGNC:11208): (Sp3 transcription factor) This gene belongs to a family of Sp1 related genes that encode transcription factors that regulate transcription by binding to consensus GC- and GT-box regulatory elements in target genes. This protein contains a zinc finger DNA-binding domain and several transactivation domains, and has been reported to function as a bifunctional transcription factor that either stimulates or represses the transcription of numerous genes. Transcript variants encoding different isoforms have been described for this gene, and one has been reported to initiate translation from a non-AUG (AUA) start codon. Additional isoforms, resulting from the use of alternate downstream translation initiation sites, have also been noted. A related pseudogene has been identified on chromosome 13. [provided by RefSeq, Feb 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.036).
• BP6: Variant 2-173910145-T-G is Benign according to our data. Variant chr2-173910145-T-G is described in ClinVar as Benign. ClinVar VariationId is 775785.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00949 (1446/152328) while in subpopulation AFR AF = 0.0329 (1367/41568). AF 95% confidence interval is 0.0314. There are 27 homozygotes in GnomAd4. There are 689 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1446 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003111.5. 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
	SP3	NM_003111.5	MANE Select	c.2142A>C	p.Thr714Thr	synonymous	Exon 7 of 7	NP_003102.1	Q02447-1
	SP3	NM_001172712.1		c.2133A>C	p.Thr711Thr	synonymous	Exon 7 of 7	NP_001166183.1	Q02447
	SP3	NM_001017371.5		c.1938A>C	p.Thr646Thr	synonymous	Exon 5 of 5	NP_001017371.3	Q02447-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP3	ENST00000310015.12	TSL:1 MANE Select	c.2142A>C	p.Thr714Thr	synonymous	Exon 7 of 7	ENSP00000310301.6	Q02447-1
	SP3	ENST00000416195.1	TSL:1	c.2010A>C	p.Thr670Thr	synonymous	Exon 5 of 5	ENSP00000413665.1	H0Y7L6
	SP3	ENST00000418194.7	TSL:1	c.1938A>C	p.Thr646Thr	synonymous	Exon 5 of 5	ENSP00000406140.3	Q02447-5

Frequencies

GnomAD3 genomes AF: 0.00949 AC: 1445 AN: 152210 Hom.: 27 Cov.: 32

Gnomad AFR AF: 0.0330

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00386

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00669

GnomAD2 exomes AF: 0.00269 AC: 674 AN: 250826 AF XY: 0.00204

Gnomad AFR exome AF: 0.0367

Gnomad AMR exome AF: 0.00174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000970

Gnomad OTH exome AF: 0.000656

GnomAD4 exome AF: 0.00105 AC: 1541 AN: 1461574 Hom.: 29 Cov.: 31 AF XY: 0.000912 AC XY: 663 AN XY: 727066

African (AFR) AF: 0.0372 AC: 1244 AN: 33470

American (AMR) AF: 0.00224 AC: 100 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.0000459 AC: 51 AN: 1111816

Other (OTH) AF: 0.00225 AC: 136 AN: 60378

GnomAD4 genome AF: 0.00949 AC: 1446 AN: 152328 Hom.: 27 Cov.: 32 AF XY: 0.00925 AC XY: 689 AN XY: 74500

African (AFR) AF: 0.0329 AC: 1367 AN: 41568

American (AMR) AF: 0.00386 AC: 59 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68020

Other (OTH) AF: 0.00662 AC: 14 AN: 2116

Alfa AF: 0.00547 Hom.: 4

Bravo AF: 0.0117

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: 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	-0.51
CADD	Benign	9.4
DANN	Benign	0.74
PhyloP100		2.9
Mutation Taster		=100/0	polymorphism

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: rs7561583; hg19: chr2-174774873;