rs371934936

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021648.5(TSPYL4):​c.949C>T​(p.Arg317Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,613,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

TSPYL4
NM_021648.5 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.74

Publications

0 publications found
Variant links:
Genes affected
TSPYL4 (HGNC:21559): (TSPY like 4) Predicted to enable chromatin binding activity and histone binding activity. Predicted to be involved in nucleosome assembly. Predicted to be active in chromatin and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07921988).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TSPYL4NM_021648.5 linkc.949C>T p.Arg317Cys missense_variant Exon 1 of 1 ENST00000420283.3 NP_067680.3 Q9UJ04

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TSPYL4ENST00000420283.3 linkc.949C>T p.Arg317Cys missense_variant Exon 1 of 1 6 NM_021648.5 ENSP00000410943.1 Q9UJ04

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152104
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000240
AC:
6
AN:
249584
AF XY:
0.0000222
show subpopulations
Gnomad AFR exome
AF:
0.0000646
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000353
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000246
AC:
36
AN:
1461888
Hom.:
0
Cov.:
29
AF XY:
0.0000179
AC XY:
13
AN XY:
727244
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.0000297
AC:
33
AN:
1112010
Other (OTH)
AF:
0.0000497
AC:
3
AN:
60392
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.465
Heterozygous variant carriers
0
2
4
7
9
11
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152104
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74294
show subpopulations
African (AFR)
AF:
0.0000483
AC:
2
AN:
41406
American (AMR)
AF:
0.00
AC:
0
AN:
15276
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5192
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4826
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10590
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
68032
Other (OTH)
AF:
0.00
AC:
0
AN:
2082
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.0000491
ESP6500AA
AF:
0.000259
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000331
AC:
4
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jun 26, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.949C>T (p.R317C) alteration is located in exon 1 (coding exon 1) of the TSPYL4 gene. This alteration results from a C to T substitution at nucleotide position 949, causing the arginine (R) at amino acid position 317 to be replaced by a cysteine (C). 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
0.26
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.37
CADD
Pathogenic
27
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0011
T
Eigen
Benign
-0.60
Eigen_PC
Benign
-0.39
FATHMM_MKL
Benign
0.39
N
LIST_S2
Benign
0.11
T
M_CAP
Benign
0.0076
T
MetaRNN
Benign
0.079
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
-0.32
N
PhyloP100
1.7
PrimateAI
Uncertain
0.72
T
PROVEAN
Benign
2.5
N
REVEL
Benign
0.23
Sift
Benign
0.44
T
Sift4G
Benign
0.21
T
Polyphen
0.017
B
Vest4
0.33
MVP
0.27
MPC
0.57
ClinPred
0.057
T
GERP RS
3.1
Varity_R
0.059
gMVP
0.58
Mutation Taster
=91/9
polymorphism

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

Other links and lift over

dbSNP: rs371934936; hg19: chr6-116574223; API