7-20784838-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_182700.6(SP8):​c.979G>A​(p.Ala327Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000343 in 1,525,688 control chromosomes in the GnomAD database, including 1 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A327G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00035 ( 1 hom. )

Consequence

SP8
NM_182700.6 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.656
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 Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.032263905).
BS2
High AC in GnomAd4 at 46 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SP8NM_182700.6 linkc.979G>A p.Ala327Thr missense_variant Exon 2 of 2 ENST00000418710.3 NP_874359.2 Q8IXZ3-4A8K350
SP8NM_198956.4 linkc.925G>A p.Ala309Thr 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.979G>A p.Ala327Thr missense_variant Exon 2 of 2 1 NM_182700.6 ENSP00000408792.2 Q8IXZ3-4
SP8ENST00000361443.4 linkc.925G>A p.Ala309Thr missense_variant Exon 3 of 3 1 ENSP00000354482.4 Q8IXZ3-3

Frequencies

GnomAD3 genomes
AF:
0.000302
AC:
46
AN:
152184
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000850
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000441
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000257
AC:
31
AN:
120526
Hom.:
0
AF XY:
0.000270
AC XY:
18
AN XY:
66608
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000297
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000466
Gnomad OTH exome
AF:
0.000804
GnomAD4 exome
AF:
0.000348
AC:
478
AN:
1373394
Hom.:
1
Cov.:
37
AF XY:
0.000338
AC XY:
229
AN XY:
677576
show subpopulations
Gnomad4 AFR exome
AF:
0.000102
Gnomad4 AMR exome
AF:
0.000315
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000256
Gnomad4 FIN exome
AF:
0.0000852
Gnomad4 NFE exome
AF:
0.000395
Gnomad4 OTH exome
AF:
0.000489
GnomAD4 genome
AF:
0.000302
AC:
46
AN:
152294
Hom.:
0
Cov.:
32
AF XY:
0.000282
AC XY:
21
AN XY:
74468
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.000849
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000441
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000357
Hom.:
0
Bravo
AF:
0.000363
ExAC
AF:
0.000136
AC:
11

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 12, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.979G>A (p.A327T) 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 979, causing the alanine (A) at amino acid position 327 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
0.13
BayesDel_addAF
Benign
-0.50
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.13
.;.;T
Eigen
Benign
-0.53
Eigen_PC
Benign
-0.41
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Benign
0.80
T;T;T
M_CAP
Benign
0.028
D
MetaRNN
Benign
0.032
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.49
.;.;N
PrimateAI
Pathogenic
0.87
D
PROVEAN
Benign
-1.1
.;N;N
REVEL
Benign
0.019
Sift
Benign
0.12
.;T;T
Sift4G
Benign
0.44
T;T;T
Polyphen
0.019
.;.;B
Vest4
0.070
MVP
0.15
ClinPred
0.039
T
GERP RS
3.1
Varity_R
0.13
gMVP
0.39

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: rs755957403; hg19: chr7-20824457; API