20-43726255-C-G

Variant summary

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

The NM_176791.4(GTSF1L):​c.440G>C​(p.Gly147Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000566 in 1,609,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

GTSF1L
NM_176791.4 missense

Scores

2
1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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=0.093422204).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GTSF1LNM_176791.4 linkc.440G>C p.Gly147Ala missense_variant Exon 1 of 1 ENST00000373003.2 NP_789761.1 Q9H1H1-1
GTSF1LNM_001008901.2 linkc.365G>C p.Gly122Ala missense_variant Exon 2 of 2 NP_001008901.1 Q9H1H1-2
GTSF1LXM_005260298.5 linkc.305G>C p.Gly102Ala 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>C p.Gly147Ala missense_variant Exon 1 of 1 6 NM_176791.4 ENSP00000362094.1 Q9H1H1-1
GTSF1LENST00000373005.2 linkc.365G>C p.Gly122Ala missense_variant Exon 2 of 2 3 ENSP00000362096.2 Q9H1H1-2

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152186
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:
0.0000241
AC:
6
AN:
248824
Hom.:
0
AF XY:
0.00000744
AC XY:
1
AN XY:
134392
show subpopulations
Gnomad AFR exome
AF:
0.00
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:
0.0000445
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.0000597
AC:
87
AN:
1456914
Hom.:
0
Cov.:
30
AF XY:
0.0000566
AC XY:
41
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:
0.0000767
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152186
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74356
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
Bravo
AF:
0.0000151
ExAC
AF:
0.0000165
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 21, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.440G>C (p.G147A) alteration is located in exon 1 (coding exon 1) of the GTSF1L gene. This alteration results from a G to C substitution at nucleotide position 440, causing the glycine (G) at amino acid position 147 to be replaced by an alanine (A). 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
0.16
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
12
DANN
Uncertain
0.99
DEOGEN2
Benign
0.010
.;T
Eigen
Benign
-0.69
Eigen_PC
Benign
-0.70
FATHMM_MKL
Benign
0.093
N
LIST_S2
Benign
0.48
T;T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.093
T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
0.81
.;L
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-0.66
N;N
REVEL
Benign
0.087
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
0.053
.;B
Vest4
0.28
MutPred
0.51
.;Gain of helix (P = 0.0696);
MVP
0.21
MPC
0.25
ClinPred
0.28
T
GERP RS
2.7
Varity_R
0.19
gMVP
0.14

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: rs749661277; hg19: chr20-42354895; API