2-173913129-T-C

Variant names:

• chr2-173913129-T-C
• NM_003111.5:c.1970A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003111.5(SP3):​c.1970A>G​(p.Tyr657Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SP3 NM_003111.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.09

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP3	NM_003111.5	c.1970A>G	p.Tyr657Cys	missense_variant	Exon 6 of 7	ENST00000310015.12	NP_003102.1
SP3	NM_001172712.1	c.1961A>G	p.Tyr654Cys	missense_variant	Exon 6 of 7		NP_001166183.1
SP3	NM_001017371.5	c.1766A>G	p.Tyr589Cys	missense_variant	Exon 4 of 5		NP_001017371.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SP3	ENST00000310015.12	c.1970A>G	p.Tyr657Cys	missense_variant	Exon 6 of 7	1	NM_003111.5	ENSP00000310301.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1970A>G (p.Y657C) alteration is located in exon 6 (coding exon 6) of the SP3 gene. This alteration results from a A to G substitution at nucleotide position 1970, causing the tyrosine (Y) at amino acid position 657 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T;T;.
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.58	D;D;D
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	1.2	L;.;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-5.6	D;D;.
REVEL	Benign	0.26
Sift	Pathogenic	0.0	D;D;.
Sift4G	Pathogenic	0.0010	D;D;.
Polyphen		0.92	P;.;.
Vest4		0.40
MutPred		0.56		Gain of disorder (P = 0.0368);.;.;
MVP		0.23
MPC		2.2
ClinPred		0.99	D
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.79
gMVP		0.89

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-174777857;