12-53328087-T-A

Position:

• chr12-53328087-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.04

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 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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SP7	NM_001173467.3	c.*59A>T		3_prime_UTR_variant	3/3	ENST00000536324.4	NP_001166938.1
SP7	NM_001300837.2	c.*59A>T		3_prime_UTR_variant	3/3		NP_001287766.1
SP7	NM_152860.2	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	c.*59A>T		3_prime_UTR_variant	3/3	2	NM_001173467.3	ENSP00000443827	P1
SP7	ENST00000303846.3	c.*59A>T		3_prime_UTR_variant	2/2	1		ENSP00000302812	P1

Frequencies

GnomAD3 genomes AF: 0.00941 AC: 1430 AN: 151982 Hom.: 15 Cov.: 32

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.: 22 AF XY: 0.0147 AC XY: 9576 AN XY: 652060

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.: 15 Cov.: 32 AF XY: 0.00928 AC XY: 690 AN XY: 74364

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.: 1

Bravo AF: 0.00919

Asia WGS AF: 0.0140 AC: 47 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	10
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

Other links and lift over

dbSNP: rs140159335; hg19: chr12-53721871;