NM_001173467.3:c.1146T>G

Variant names:

• chr12-53328296-A-C
• rs1944656837
• NM_001173467.3:c.1146T>G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001173467.3(SP7):​c.1146T>G​(p.Gly382Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00002 in 150,254 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SP7 NM_001173467.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.72

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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BP7: Synonymous conserved (PhyloP=-5.72 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP7	NM_001173467.3	c.1146T>G	p.Gly382Gly	synonymous_variant	Exon 3 of 3	ENST00000536324.4	NP_001166938.1
SP7	NM_152860.2	c.1146T>G	p.Gly382Gly	synonymous_variant	Exon 2 of 2		NP_690599.1
SP7	NM_001300837.2	c.1092T>G	p.Gly364Gly	synonymous_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.1146T>G	p.Gly382Gly	synonymous_variant	Exon 3 of 3	2	NM_001173467.3	ENSP00000443827.2
SP7	ENST00000303846.3	c.1146T>G	p.Gly382Gly	synonymous_variant	Exon 2 of 2	1		ENSP00000302812.3
SP7	ENST00000537210.2	c.1092T>G	p.Gly364Gly	synonymous_variant	Exon 2 of 2	1		ENSP00000441367.2

Frequencies

GnomAD3 genomes AF: 0.0000200 AC: 3 AN: 150254 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000245

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000297

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1458062 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 725032

Gnomad4 AFR exome AF: 0.00

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 AF: 0.0000200 AC: 3 AN: 150254 Hom.: 0 Cov.: 32 AF XY: 0.0000273 AC XY: 2 AN XY: 73328

Gnomad4 AFR AF: 0.0000245

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000297

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.34
DANN	Benign	0.57

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

LitVar

Other links and lift over

dbSNP: rs1944656837; hg19: chr12-53722080;