7-105468381-T-C

Position:

• chr7-105468381-T-C

Variant summary

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

The NM_019042.5(PUS7):​c.1481A>G​(p.Asp494Gly) 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. 13/23 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: 5.10

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PUS7	NM_019042.5	c.1481A>G	p.Asp494Gly	missense_variant	12/16	ENST00000469408.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PUS7	ENST00000469408.6	c.1481A>G	p.Asp494Gly	missense_variant	12/16	1	NM_019042.5	P1
PUS7	ENST00000356362.6	c.1481A>G	p.Asp494Gly	missense_variant	12/16	2		P1
PUS7	ENST00000481939.5	c.*61A>G		3_prime_UTR_variant, NMD_transcript_variant	12/17	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 20, 2023

The c.1481A>G (p.D494G) alteration is located in exon 12 (coding exon 11) of the PUS7 gene. This alteration results from a A to G substitution at nucleotide position 1481, causing the aspartic acid (D) at amino acid position 494 to be replaced by a glycine (G). 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	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.059	T;T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.48
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.94	.;D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N
MutationTaster	Benign	0.75	N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.11
Sift	Uncertain	0.021	D;D
Sift4G	Benign	0.28	T;T
Polyphen		0.033	B;B
Vest4		0.35
MutPred		0.47		Loss of stability (P = 0.0552);Loss of stability (P = 0.0552);
MVP		0.33
MPC		0.30
ClinPred		0.44	T
GERP RS		3.1
Varity_R		0.27
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.25		Position offset: -44

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: chr7-105108828;