Variant 12-53328258-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001173467.3(SP7):c.1184G>A(p.Arg395His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000252 in 1,611,352 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R395C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00026 ( 4 hom. )

Consequence

SP7
NM_001173467.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.421

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004576415).

BP6

Variant 12-53328258-C-T is Benign according to our data. Variant chr12-53328258-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1587263.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SP7	NM_001173467.3 linkuse as main transcript	c.1184G>A	p.Arg395His	missense_variant	3/3	ENST00000536324.4
SP7	NM_152860.2 linkuse as main transcript	c.1184G>A	p.Arg395His	missense_variant	2/2
SP7	NM_001300837.2 linkuse as main transcript	c.1130G>A	p.Arg377His	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SP7	ENST00000536324.4 linkuse as main transcript	c.1184G>A	p.Arg395His	missense_variant	3/3	2	NM_001173467.3	P1	Q8TDD2-1
SP7	ENST00000303846.3 linkuse as main transcript	c.1184G>A	p.Arg395His	missense_variant	2/2	1		P1	Q8TDD2-1
SP7	ENST00000537210.2 linkuse as main transcript	c.1130G>A	p.Arg377His	missense_variant	2/2	1			Q8TDD2-2

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000542

AC:

132

AN:

243614

Hom.:

AF XY:

0.000747

AC XY:

AN XY:

132472

show subpopulations

Gnomad AFR exome

AF:

0.000131

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00412

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000274

Gnomad OTH exome

AF:

0.000508

GnomAD4 exome

AF:

0.000265

AC:

386

AN:

1459122

Hom.:

Cov.:

AF XY:

0.000402

AC XY:

292

AN XY:

725786

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00418

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.000183

GnomAD4 genome

AF:

0.000131

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000550

Hom.:

Bravo

AF:

0.0000416

ESP6500AA

AF:

0.000256

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000612

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Osteogenesis imperfecta

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Apr 01, 2019

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Nov 12, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.24

T;T;.

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.45

M_CAP

Benign

0.0061

MetaRNN

Benign

0.0046

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

N;N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.65

PROVEAN

Benign

0.35

N;N;N

REVEL

Benign

0.079

Sift

Benign

0.17

T;T;T

Sift4G

Benign

0.12

T;T;T

Polyphen

0.99

D;D;.

Vest4

0.21

MVP

0.20

MPC

0.56

ClinPred

0.023

GERP RS

2.6

Varity_R

0.043

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