6-116253060-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_021648.5(TSPYL4):​c.949C>G​(p.Arg317Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,888 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. R317C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TSPYL4
NM_021648.5 missense

Scores

1
2
16

Clinical Significance

Not reported in ClinVar

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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.41903317).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TSPYL4NM_021648.5 linkc.949C>G p.Arg317Gly 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>G p.Arg317Gly missense_variant Exon 1 of 1 6 NM_021648.5 ENSP00000410943.1 Q9UJ04

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461888
Hom.:
0
Cov.:
29
AF XY:
0.00000138
AC XY:
1
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:
0.0000187
AC:
1
AN:
53420
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1112010
Other (OTH)
AF:
0.00
AC:
0
AN:
60392
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.64
BayesDel_addAF
Benign
-0.021
T
BayesDel_noAF
Benign
-0.27
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0055
T
Eigen
Benign
0.14
Eigen_PC
Benign
0.13
FATHMM_MKL
Benign
0.68
D
LIST_S2
Benign
0.26
T
M_CAP
Benign
0.0095
T
MetaRNN
Benign
0.42
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
1.0
L
PhyloP100
1.7
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-2.1
N
REVEL
Benign
0.23
Sift
Benign
0.10
T
Sift4G
Benign
0.22
T
Polyphen
0.97
D
Vest4
0.45
MutPred
0.59
Loss of stability (P = 0.0188);
MVP
0.46
MPC
1.2
ClinPred
0.78
D
GERP RS
3.1
Varity_R
0.15
gMVP
0.69
Mutation Taster
=83/17
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