rs377532102

Variant names:

• chr12-53328289-G-A
• NM_001173467.3:c.1153C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-53328289-G-A
• chr12-53328289-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001173467.3(SP7):​c.1153C>T​(p.Pro385Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,900 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SP7 NM_001173467.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.975

Genes affected

SP7 (HGNC:17321): (Sp7 transcription factor) This gene encodes a member of the Sp subfamily of Sp/XKLF transcription factors. Sp family proteins are sequence-specific DNA-binding proteins characterized by an amino-terminal trans-activation domain and three carboxy-terminal zinc finger motifs. This protein is a bone specific transcription factor and is required for osteoblast differentiation and bone formation.[provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04356557).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP7	NM_001173467.3	c.1153C>T	p.Pro385Ser	missense_variant	Exon 3 of 3	ENST00000536324.4	NP_001166938.1
SP7	NM_152860.2	c.1153C>T	p.Pro385Ser	missense_variant	Exon 2 of 2		NP_690599.1
SP7	NM_001300837.2	c.1099C>T	p.Pro367Ser	missense_variant	Exon 3 of 3		NP_001287766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SP7	ENST00000536324.4	c.1153C>T	p.Pro385Ser	missense_variant	Exon 3 of 3	2	NM_001173467.3	ENSP00000443827.2
SP7	ENST00000303846.3	c.1153C>T	p.Pro385Ser	missense_variant	Exon 2 of 2	1		ENSP00000302812.3
SP7	ENST00000537210.2	c.1099C>T	p.Pro367Ser	missense_variant	Exon 2 of 2	1		ENSP00000441367.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1458900 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 725550

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	3.0
DANN	Benign	0.88
DEOGEN2	Benign	0.19	T;T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.33	.;T;T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.044	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.0	N;N;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	0.82	N;N;N
REVEL	Benign	0.021
Sift	Benign	0.46	T;T;T
Sift4G	Benign	0.74	T;T;T
Polyphen		0.0010	B;B;.
Vest4		0.19
MutPred		0.17		Gain of phosphorylation at P385 (P = 0.0034);Gain of phosphorylation at P385 (P = 0.0034);.;
MVP		0.11
MPC		0.30
ClinPred		0.035	T
GERP RS		-2.5
Varity_R		0.023

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: chr12-53722073; COSMIC: COSV105156292; COSMIC: COSV105156292;