chr7-105462747-T-C

Position:

• chr7-105462747-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019042.5(PUS7):​c.1631A>G​(p.Gln544Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PUS7 NM_019042.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.77

Genes affected

PUS7 (HGNC:26033): (pseudouridine synthase 7) Enables enzyme binding activity and pseudouridine synthase activity. Involved in several processes, including pseudouridine synthesis; regulation of hematopoietic stem cell differentiation; and regulation of mesoderm development. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.083159596).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PUS7	NM_019042.5	c.1631A>G	p.Gln544Arg	missense_variant	14/16	ENST00000469408.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PUS7	ENST00000469408.6	c.1631A>G	p.Gln544Arg	missense_variant	14/16	1	NM_019042.5	P1
PUS7	ENST00000356362.6	c.1631A>G	p.Gln544Arg	missense_variant	14/16	2		P1
PUS7	ENST00000481939.5	c.*211A>G		3_prime_UTR_variant, NMD_transcript_variant	14/17	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Oct 12, 2023

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	18
DANN	Benign	0.88
DEOGEN2	Benign	0.018	T;T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.59	.;T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.083	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.5	N;N
MutationTaster	Benign	0.99	N;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.26	N;N
REVEL	Benign	0.063
Sift	Benign	0.50	T;T
Sift4G	Benign	0.49	T;T
Polyphen		0.0	B;B
Vest4		0.12
MutPred		0.50		Loss of methylation at K540 (P = 0.1224);Loss of methylation at K540 (P = 0.1224);
MVP		0.30
MPC		0.23
ClinPred		0.37	T
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.066
gMVP		0.73

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-105103194;