12-43738324-T-C

Position:

• chr12-43738324-T-C

Variant summary

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

The NM_031292.5(PUS7L):​c.1430A>G​(p.Tyr477Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000709 in 1,411,010 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: PUS7L NM_031292.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.39

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.1430A>G	p.Tyr477Cys	missense_variant	6/9	ENST00000344862.10	NP_112582.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PUS7L	ENST00000344862.10	c.1430A>G	p.Tyr477Cys	missense_variant	6/9	1	NM_031292.5	ENSP00000343081.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.09e-7 AC: 1 AN: 1411010 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 705306

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: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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 10, 2024

The c.1430A>G (p.Y477C) alteration is located in exon 6 (coding exon 5) of the PUS7L gene. This alteration results from a A to G substitution at nucleotide position 1430, causing the tyrosine (Y) at amino acid position 477 to be replaced by a cysteine (C). 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	0.15
BayesDel_addAF	Benign	-0.0000059	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.042	T;T;T;.
Eigen	Benign	0.050
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.93	.;.;D;D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.62	D;D;D;D
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	2.0	M;M;M;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-5.1	D;D;D;D
REVEL	Benign	0.15
Sift	Benign	0.11	T;T;T;T
Sift4G	Uncertain	0.0060	D;D;D;D
Polyphen		0.32	B;B;B;.
Vest4		0.74
MutPred		0.58		Gain of methylation at K476 (P = 0.0124);Gain of methylation at K476 (P = 0.0124);Gain of methylation at K476 (P = 0.0124);.;
MVP		0.60
MPC		0.059
ClinPred		0.94	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.48
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr12-44132127;