rs749661277

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_176791.4(GTSF1L):​c.440G>T​(p.Gly147Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,456,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. G147A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

GTSF1L
NM_176791.4 missense

Scores

2
1
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.297
Variant links:
Genes affected
GTSF1L (HGNC:16198): (gametocyte specific factor 1 like) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.18733597).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GTSF1LNM_176791.4 linkc.440G>T p.Gly147Val missense_variant Exon 1 of 1 ENST00000373003.2 NP_789761.1 Q9H1H1-1
GTSF1LNM_001008901.2 linkc.365G>T p.Gly122Val missense_variant Exon 2 of 2 NP_001008901.1 Q9H1H1-2
GTSF1LXM_005260298.5 linkc.305G>T p.Gly102Val missense_variant Exon 2 of 2 XP_005260355.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GTSF1LENST00000373003.2 linkc.440G>T p.Gly147Val missense_variant Exon 1 of 1 6 NM_176791.4 ENSP00000362094.1 Q9H1H1-1
GTSF1LENST00000373005.2 linkc.365G>T p.Gly122Val missense_variant Exon 2 of 2 3 ENSP00000362096.2 Q9H1H1-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1456916
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
724364
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
9.02e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.20
BayesDel_addAF
Benign
-0.069
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Benign
0.020
.;T
Eigen
Benign
-0.30
Eigen_PC
Benign
-0.42
FATHMM_MKL
Benign
0.10
N
LIST_S2
Benign
0.47
T;T
M_CAP
Benign
0.030
D
MetaRNN
Benign
0.19
T;T
MetaSVM
Benign
-0.80
T
MutationAssessor
Benign
1.4
.;L
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-2.0
N;N
REVEL
Benign
0.17
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
0.93
.;P
Vest4
0.36
MutPred
0.53
.;Gain of MoRF binding (P = 0.0699);
MVP
0.52
MPC
0.26
ClinPred
0.85
D
GERP RS
2.7
Varity_R
0.21
gMVP
0.21

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-42354895; API