20-43726460-T-G

Variant names:

• chr20-43726460-T-G
• rs754528433
• NM_176791.4:c.235A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_176791.4(GTSF1L):​c.235A>C​(p.Lys79Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. K79E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: GTSF1L NM_176791.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.120
• 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_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047322273).

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.235A>C	p.Lys79Gln	missense	Exon 1 of 1	NP_789761.1	Q9H1H1-1
	GTSF1L	NM_001008901.2		c.235A>C	p.Lys79Gln	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.235A>C	p.Lys79Gln	missense	Exon 1 of 1	ENSP00000362094.1	Q9H1H1-1
	GTSF1L	ENST00000373005.2	TSL:3	c.235A>C	p.Lys79Gln	missense	Exon 1 of 2	ENSP00000362096.2	Q9H1H1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461892 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.1
DANN	Benign	0.75
DEOGEN2	Benign	0.0059	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L
PhyloP100		0.12
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.019
Sift	Benign	0.39	T
Sift4G	Benign	0.58	T
Polyphen		0.11	B
Vest4		0.18
MutPred		0.38		Loss of ubiquitination at K79 (P = 9e-04)
MVP		0.014
MPC		0.033
ClinPred		0.049	T
GERP RS		-0.31
PromoterAI		-0.011	Neutral
Varity_R		0.062
gMVP		0.22
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs754528433; hg19: chr20-42355100;