chr20-43726391-C-A

Variant names:

• chr20-43726391-C-A
• rs762812139
• NM_176791.4:c.304G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_176791.4(GTSF1L):​c.304G>T​(p.Asp102Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 15/22 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. D102N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GTSF1L NM_176791.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.785
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.304G>T	p.Asp102Tyr	missense	Exon 1 of 1	NP_789761.1	Q9H1H1-1
	GTSF1L	NM_001008901.2		c.279+25G>T		intron	N/A	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.304G>T	p.Asp102Tyr	missense	Exon 1 of 1	ENSP00000362094.1	Q9H1H1-1
	GTSF1L	ENST00000373005.2	TSL:3	c.279+25G>T		intron	N/A	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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.061	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.79
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.24
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.99	D
Vest4		0.48
MutPred		0.64		Loss of disorder (P = 0.0223)
MVP		0.31
MPC		0.24
ClinPred		0.84	D
GERP RS		3.0
PromoterAI		-0.011	Neutral
Varity_R		0.12
gMVP		0.39
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs762812139; hg19: chr20-42355031;