Variant 12-53328143-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001173467.3(SP7):c.*3C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000392 in 1,605,978 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

SP7
NM_001173467.3 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.354

Variant links:

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]

SP7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 (BayesDel_noAF=-0.6).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
SP7	NM_001173467.3 linkuse as main transcript	c.*3C>T	3_prime_UTR_variant	3/3	ENST00000536324.4	NP_001166938.1
SP7	NM_001300837.2 linkuse as main transcript	c.*3C>T	3_prime_UTR_variant	3/3		NP_001287766.1
SP7	NM_152860.2 linkuse as main transcript	c.*3C>T	3_prime_UTR_variant	2/2		NP_690599.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SP7	ENST00000536324.4 linkuse as main transcript	c.*3C>T	3_prime_UTR_variant	3/3	2	NM_001173467.3	ENSP00000443827	P1	Q8TDD2-1
SP7	ENST00000303846.3 linkuse as main transcript	c.*3C>T	3_prime_UTR_variant	2/2	1		ENSP00000302812	P1	Q8TDD2-1
SP7	ENST00000537210.2 linkuse as main transcript		downstream_gene_variant		1		ENSP00000441367		Q8TDD2-2

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000984

AC:

AN:

233834

Hom.:

AF XY:

0.000141

AC XY:

AN XY:

128084

show subpopulations

Gnomad AFR exome

AF:

0.000150

Gnomad AMR exome

AF:

0.000182

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000478

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000953

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000392

AC:

AN:

1453824

Hom.:

Cov.:

AF XY:

0.0000595

AC XY:

AN XY:

722824

show subpopulations

Gnomad4 AFR exome

AF:

0.0000601

Gnomad4 AMR exome

AF:

0.000115

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000411

Gnomad4 FIN exome

AF:

0.0000193

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000666

Hom.:

Bravo

AF:

0.0000604

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Jul 18, 2024

Variant summary: SP7 c.*3C>T is located in the untranslated mRNA region downstream of the termination codon. The variant allele was found at a frequency of 9.8e-05 in 233834 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in SP7 causing Osteogenesis Imperfecta Type 12, allowing no conclusion about variant significance. To our knowledge, no occurrence of c.*3C>T in individuals affected with Osteogenesis Imperfecta Type 12 and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

7.2

DANN

Benign

0.83

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over