12-43742507-T-A

Position:

• chr12-43742507-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_031292.5(PUS7L):​c.1312A>T​(p.Arg438Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PUS7L NM_031292.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.47

Genes affected

PUS7L (HGNC:25276): (pseudouridine synthase 7 like) Predicted to enable pseudouridine synthase activity. Predicted to be involved in pseudouridine synthesis. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

PUS7L (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PUS7L	NM_031292.5	c.1312A>T	p.Arg438Trp	missense_variant	5/9	ENST00000344862.10	NP_112582.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PUS7L	ENST00000344862.10	c.1312A>T	p.Arg438Trp	missense_variant	5/9	1	NM_031292.5	ENSP00000343081.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 26, 2024

The c.1312A>T (p.R438W) alteration is located in exon 5 (coding exon 4) of the PUS7L gene. This alteration results from a A to T substitution at nucleotide position 1312, causing the arginine (R) at amino acid position 438 to be replaced by a tryptophan (W). 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	0.14
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.040	T;T;T;.;T;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.95	.;.;D;D;D;D
M_CAP	Benign	0.085	D
MetaRNN	Uncertain	0.61	D;D;D;D;D;D
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.9	M;M;M;.;.;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.0	N;N;N;N;N;N
REVEL	Uncertain	0.31
Sift	Uncertain	0.020	D;D;D;D;D;D
Sift4G	Uncertain	0.010	D;D;D;D;.;D
Polyphen		0.99	D;D;D;.;.;.
Vest4		0.29
MutPred		0.66		Gain of catalytic residue at R433 (P = 0.0024);Gain of catalytic residue at R433 (P = 0.0024);Gain of catalytic residue at R433 (P = 0.0024);.;.;.;
MVP		0.65
MPC		0.20
ClinPred		0.96	D
GERP RS		2.0
Varity_R		0.041
gMVP		0.52

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-44136310;