20-43726567-C-T

Variant names:

• chr20-43726567-C-T
• rs762003145
• NM_176791.4:c.128G>A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_176791.4(GTSF1L):​c.128G>A​(p.Cys43Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GTSF1L NM_176791.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.43
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.988

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_176791.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTSF1L	NM_176791.4	MANE Select	c.128G>A	p.Cys43Tyr	missense	Exon 1 of 1	NP_789761.1	Q9H1H1-1
	GTSF1L	NM_001008901.2		c.128G>A	p.Cys43Tyr	missense	Exon 1 of 2	NP_001008901.1	Q9H1H1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTSF1L	ENST00000373003.2	TSL:6 MANE Select	c.128G>A	p.Cys43Tyr	missense	Exon 1 of 1	ENSP00000362094.1	Q9H1H1-1
	GTSF1L	ENST00000373005.2	TSL:3	c.128G>A	p.Cys43Tyr	missense	Exon 1 of 2	ENSP00000362096.2	Q9H1H1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.51	D
BayesDel_noAF	Pathogenic	0.49
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.75	T
M_CAP	Uncertain	0.19	D
MetaRNN	Pathogenic	0.99	D
MetaSVM	Pathogenic	0.85	D
MutationAssessor	Pathogenic	3.0	M
PhyloP100		1.4
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-11	D
REVEL	Pathogenic	0.91
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.90
MutPred		0.92		Gain of phosphorylation at C43 (P = 0.0602)
MVP		0.93
MPC		0.29
ClinPred		1.0	D
GERP RS		3.7
PromoterAI		0.028	Neutral
Varity_R		0.93
gMVP		0.75
Mutation Taster		=40/60	disease causing

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

Other links and lift over

dbSNP: rs762003145; hg19: chr20-42355207;