7-20784792-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_182700.6(SP8):​c.1025G>A​(p.Arg342His) variant causes a missense change. The variant allele was found at a frequency of 0.000000722 in 1,384,476 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: not found (cov: 32)
Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

SP8
NM_182700.6 missense

Scores

4
9
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.65
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 Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.27386796).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SP8NM_182700.6 linkc.1025G>A p.Arg342His missense_variant Exon 2 of 2 ENST00000418710.3 NP_874359.2 Q8IXZ3-4A8K350
SP8NM_198956.4 linkc.971G>A p.Arg324His 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.1025G>A p.Arg342His missense_variant Exon 2 of 2 1 NM_182700.6 ENSP00000408792.2 Q8IXZ3-4
SP8ENST00000361443.4 linkc.971G>A p.Arg324His missense_variant Exon 3 of 3 1 ENSP00000354482.4 Q8IXZ3-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000758
AC:
1
AN:
131878
Hom.:
0
AF XY:
0.0000137
AC XY:
1
AN XY:
72850
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000994
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
7.22e-7
AC:
1
AN:
1384476
Hom.:
0
Cov.:
37
AF XY:
0.00000146
AC XY:
1
AN XY:
684014
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000282
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 21, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1025G>A (p.R342H) 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 1025, causing the arginine (R) at amino acid position 342 to be replaced by a histidine (H). 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
Pathogenic
0.68
BayesDel_addAF
Benign
-0.093
T
BayesDel_noAF
Benign
-0.37
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.54
.;.;D
Eigen
Uncertain
0.34
Eigen_PC
Uncertain
0.28
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Pathogenic
0.97
D;D;D
M_CAP
Uncertain
0.17
D
MetaRNN
Benign
0.27
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.9
.;.;M
PrimateAI
Pathogenic
0.95
D
PROVEAN
Pathogenic
-4.5
.;D;D
REVEL
Benign
0.16
Sift
Uncertain
0.0020
.;D;D
Sift4G
Uncertain
0.0070
D;D;D
Polyphen
0.96
.;.;P
Vest4
0.29
MutPred
0.45
.;.;Loss of MoRF binding (P = 0.0142);
MVP
0.27
ClinPred
0.98
D
GERP RS
3.3
Varity_R
0.67
gMVP
0.73

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.

Other links and lift over

dbSNP: rs1324645918; hg19: chr7-20824411; API