Genetic Variant GTSF1L:p.Gly147Ala (chr20-43726255-C-G) – ACMG Classification: Uncertain_significance (0 pts)

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

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]

GTSF1L links:

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
GTSF1L	NM_176791.4 link	c.440G>C	p.Gly147Ala	missense_variant	Exon 1 of 1	ENST00000373003.2	NP_789761.1	Q9H1H1-1
GTSF1L	NM_001008901.2 link	c.365G>C	p.Gly122Ala	missense_variant	Exon 2 of 2		NP_001008901.1	Q9H1H1-2
GTSF1L	XM_005260298.5 link	c.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
GTSF1L	ENST00000373003.2 link	c.440G>C	p.Gly147Ala	missense_variant	Exon 1 of 1	6	NM_176791.4	ENSP00000362094.1		Q9H1H1-1
GTSF1L	ENST00000373005.2 link	c.365G>C	p.Gly122Ala	missense_variant	Exon 2 of 2	3		ENSP00000362096.2		Q9H1H1-2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152186

Hom.:

Cov.:

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:

AN:

248824

Hom.:

AF XY:

0.00000744

AC XY:

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:

AN:

1456914

Hom.:

Cov.:

AF XY:

0.0000566

AC XY:

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:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

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:

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

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.010

.;T

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.093

LIST_S2

Benign

0.48

T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.093

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.81

.;L

PrimateAI

Benign

0.38

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over