NM_015001.3:c.496G>T

Variant summary

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

The NM_015001.3(SPEN):​c.496G>T​(p.Asp166Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,613,896 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D166N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SPEN
NM_015001.3 missense

Scores

2
10
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.72
Variant links:
Genes affected
SPEN (HGNC:17575): (spen family transcriptional repressor) This gene encodes a hormone inducible transcriptional repressor. Repression of transcription by this gene product can occur through interactions with other repressors, by the recruitment of proteins involved in histone deacetylation, or through sequestration of transcriptional activators. The product of this gene contains a carboxy-terminal domain that permits binding to other corepressor proteins. This domain also permits interaction with members of the NuRD complex, a nucleosome remodeling protein complex that contains deacetylase activity. In addition, this repressor contains several RNA recognition motifs that confer binding to a steroid receptor RNA coactivator; this binding can modulate the activity of both liganded and nonliganded steroid receptors. [provided by RefSeq, Jul 2008]

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=0.3291059).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SPENNM_015001.3 linkc.496G>T p.Asp166Tyr missense_variant Exon 3 of 15 ENST00000375759.8 NP_055816.2 Q96T58

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SPENENST00000375759.8 linkc.496G>T p.Asp166Tyr missense_variant Exon 3 of 15 1 NM_015001.3 ENSP00000364912.3 Q96T58

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152022
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251428
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135896
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461874
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
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
AF:
0.00000658
AC:
1
AN:
152022
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74254
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000192
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.90
BayesDel_addAF
Uncertain
0.019
T
BayesDel_noAF
Benign
-0.13
CADD
Pathogenic
30
DANN
Uncertain
0.99
DEOGEN2
Benign
0.31
T;T
Eigen
Uncertain
0.58
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.91
D;D
M_CAP
Benign
0.0098
T
MetaRNN
Benign
0.33
T;T
MetaSVM
Benign
-0.80
T
MutationAssessor
Benign
0.55
N;.
PrimateAI
Pathogenic
0.80
T
PROVEAN
Uncertain
-2.8
D;D
REVEL
Uncertain
0.32
Sift
Uncertain
0.0010
D;D
Sift4G
Uncertain
0.0040
D;D
Polyphen
1.0
D;.
Vest4
0.85
MutPred
0.34
Gain of MoRF binding (P = 0.0312);.;
MVP
0.54
MPC
2.0
ClinPred
0.79
D
GERP RS
5.8
Varity_R
0.45
gMVP
0.62

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: rs988492642; hg19: chr1-16202788; API