rs778021564

Variant names:

• chr12-53382308-A-C
• rs778021564
• NM_138473.3:c.361A>C

Your query was ambiguous. Multiple possible variants found:

• chr12-53382308-A-C
• chr12-53382308-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138473.3(SP1):​c.361A>C​(p.Lys121Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K121E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SP1 NM_138473.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.61

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22184345).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP1	NM_138473.3	c.361A>C	p.Lys121Gln	missense_variant	Exon 3 of 6	ENST00000327443.9	NP_612482.2
SP1	NM_003109.1	c.340A>C	p.Lys114Gln	missense_variant	Exon 3 of 6		NP_003100.1
SP1	NM_001251825.2	c.217A>C	p.Lys73Gln	missense_variant	Exon 3 of 6		NP_001238754.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SP1	ENST00000327443.9	c.361A>C	p.Lys121Gln	missense_variant	Exon 3 of 6	1	NM_138473.3	ENSP00000329357.4
SP1	ENST00000426431.2	c.340A>C	p.Lys114Gln	missense_variant	Exon 3 of 6	1		ENSP00000404263.2
SP1	ENST00000548560.1	c.340A>C	p.Lys114Gln	missense_variant	Exon 2 of 2	2		ENSP00000458133.1
SP1	ENST00000551969.5	c.217A>C	p.Lys73Gln	missense_variant	Exon 3 of 3	3		ENSP00000457804.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T;T;.;.
Eigen	Benign	0.036
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.81	T;T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.22	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	.;L;.;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-2.2	N;N;N;N
REVEL	Benign	0.088
Sift	Uncertain	0.0020	D;D;D;D
Sift4G	Benign	0.61	T;T;T;T
Polyphen		0.14	.;B;.;.
Vest4		0.42, 0.41
MutPred		0.26		.;Loss of ubiquitination at K121 (P = 0.0071);.;.;
MVP		0.55
MPC		0.31
ClinPred		0.87	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs778021564; hg19: chr12-53776092;