rs374429537

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_001326543.2(SP4):​c.-569C>G variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00000434 in 1,613,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SP4
NM_001326543.2 5_prime_UTR_premature_start_codon_gain

Scores

2
9
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.17
Variant links:
Genes affected
SP4 (HGNC:11209): (Sp4 transcription factor) The protein encoded by this gene is a transcription factor that can bind to the GC promoter region of a variety of genes, including those of the photoreceptor signal transduction system. The encoded protein binds to the same sites in promoter CpG islands as does the transcription factor SP1, although its expression is much more restricted compared to that of SP1. This gene may be involved in bipolar disorder and schizophrenia. [provided by RefSeq, May 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.26714522).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SP4NM_003112.5 linkc.371C>G p.Ser124Trp missense_variant Exon 3 of 6 ENST00000222584.8 NP_003103.2 Q02446

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SP4ENST00000222584.8 linkc.371C>G p.Ser124Trp missense_variant Exon 3 of 6 1 NM_003112.5 ENSP00000222584.3 Q02446
SP4ENST00000649633.1 linkc.320C>G p.Ser107Trp missense_variant Exon 3 of 6 ENSP00000496957.1 A0A3B3IRW4
SP4ENST00000432066.2 linkc.7+1278C>G intron_variant Intron 1 of 1 5 ENSP00000393623.2 C9JUS7
SP4ENST00000448246.1 linkn.123+744C>G intron_variant Intron 2 of 4 5 ENSP00000390817.1 F8WB93

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152184
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251468
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135916
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
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:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461594
Hom.:
0
Cov.:
35
AF XY:
0.00000275
AC XY:
2
AN XY:
727110
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152184
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000540
Hom.:
0
Bravo
AF:
0.00000378
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000165
AC:
2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.63
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.41
CADD
Uncertain
26
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.61
D;.
Eigen
Uncertain
0.25
Eigen_PC
Uncertain
0.36
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.90
D;D
M_CAP
Benign
0.0074
T
MetaRNN
Benign
0.27
T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
1.2
L;.
PrimateAI
Uncertain
0.57
T
PROVEAN
Uncertain
-2.5
D;.
REVEL
Benign
0.16
Sift
Uncertain
0.0010
D;.
Sift4G
Uncertain
0.015
D;.
Polyphen
0.89
P;.
Vest4
0.51
MVP
0.14
MPC
0.13
ClinPred
0.69
D
GERP RS
4.5
Varity_R
0.31
gMVP
0.23

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: rs374429537; hg19: chr7-21469154; API