Variant chr12-53328087-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001173467.3(SP7):c.*59A>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 0.0134 in 1,477,294 control chromosomes in the GnomAD database, including 226 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0094 ( 15 hom., cov: 32)

Exomes 𝑓: 0.014 ( 211 hom. )

Consequence

SP7
NM_001173467.3 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.04

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 12-53328087-T-A is Benign according to our data. Variant chr12-53328087-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 309759.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0094 (1429/152098) while in subpopulation SAS AF= 0.0404 (194/4804). AF 95% confidence interval is 0.0357. There are 15 homozygotes in gnomad4. There are 690 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
SP7	NM_001173467.3 linkuse as main transcript	c.*59A>T	3_prime_UTR_variant	3/3	ENST00000536324.4	NP_001166938.1
SP7	NM_001300837.2 linkuse as main transcript	c.*59A>T	3_prime_UTR_variant	3/3		NP_001287766.1
SP7	NM_152860.2 linkuse as main transcript	c.*59A>T	3_prime_UTR_variant	2/2		NP_690599.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SP7	ENST00000536324.4 linkuse as main transcript	c.*59A>T		3_prime_UTR_variant	3/3	2	NM_001173467.3	ENSP00000443827	P1	Q8TDD2-1
SP7	ENST00000303846.3 linkuse as main transcript	c.*59A>T		3_prime_UTR_variant	2/2	1		ENSP00000302812	P1	Q8TDD2-1

Frequencies

GnomAD3 genomes

AF:

0.00941

AC:

1430

AN:

151982

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00235

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.00852

Gnomad ASJ

AF:

0.00893

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0403

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0138

Gnomad OTH

AF:

0.00766

GnomAD4 exome

AF:

0.0139

AC:

18388

AN:

1325196

Hom.:

211

Cov.:

AF XY:

0.0147

AC XY:

9576

AN XY:

652060

show subpopulations

Gnomad4 AFR exome

AF:

0.00196

Gnomad4 AMR exome

AF:

0.00712

Gnomad4 ASJ exome

AF:

0.00954

Gnomad4 EAS exome

AF:

0.000111

Gnomad4 SAS exome

AF:

0.0428

Gnomad4 FIN exome

AF:

0.00207

Gnomad4 NFE exome

AF:

0.0134

Gnomad4 OTH exome

AF:

0.0136

GnomAD4 genome

AF:

0.00940

AC:

1429

AN:

152098

Hom.:

Cov.:

AF XY:

0.00928

AC XY:

690

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.00234

Gnomad4 AMR

AF:

0.00851

Gnomad4 ASJ

AF:

0.00893

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0404

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.0138

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.00974

Hom.:

Bravo

AF:

0.00919

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 31, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.71

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