7-20784367-C-T

Variant summary

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

The NM_182700.6(SP8):​c.1450G>A​(p.Ala484Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000146 in 1,372,568 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

SP8
NM_182700.6 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.200
Variant links:
Genes affected
SP8 (HGNC:19196): (Sp8 transcription factor) The protein encoded by this gene is an SP family transcription factor that in mouse has been shown to be essential for proper limb development. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2011]

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 (MetaRNN=0.0417279).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SP8NM_182700.6 linkc.1450G>A p.Ala484Thr missense_variant Exon 2 of 2 ENST00000418710.3 NP_874359.2 Q8IXZ3-4A8K350
SP8NM_198956.4 linkc.1396G>A p.Ala466Thr missense_variant Exon 3 of 3 NP_945194.1 Q8IXZ3-3A8K350

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SP8ENST00000418710.3 linkc.1450G>A p.Ala484Thr missense_variant Exon 2 of 2 1 NM_182700.6 ENSP00000408792.2 Q8IXZ3-4
SP8ENST00000361443.4 linkc.1396G>A p.Ala466Thr missense_variant Exon 3 of 3 1 ENSP00000354482.4 Q8IXZ3-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000146
AC:
2
AN:
1372568
Hom.:
0
Cov.:
37
AF XY:
0.00000295
AC XY:
2
AN XY:
677182
show subpopulations
Gnomad4 AFR exome
AF:
0.0000335
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:
9.30e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 07, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1450G>A (p.A484T) alteration is located in exon 2 (coding exon 2) of the SP8 gene. This alteration results from a G to A substitution at nucleotide position 1450, causing the alanine (A) at amino acid position 484 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.096
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.079
.;.;T
Eigen
Benign
-0.69
Eigen_PC
Benign
-0.54
FATHMM_MKL
Benign
0.23
N
LIST_S2
Benign
0.67
T;T;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.042
T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
0.20
.;.;N
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
-0.50
.;N;N
REVEL
Benign
0.065
Sift
Benign
0.48
.;T;T
Sift4G
Benign
0.58
T;T;T
Polyphen
0.14
.;.;B
Vest4
0.12
MutPred
0.33
.;.;Gain of glycosylation at A466 (P = 0.0118);
MVP
0.11
ClinPred
0.21
T
GERP RS
3.7
Varity_R
0.074
gMVP
0.50

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-20823986; API