chr7-105472173-C-T

Position:

• chr7-105472173-C-T

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_019042.5(PUS7):​c.1196G>A​(p.Trp399Ter) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PUS7 NM_019042.5 stop_gained
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 7.10

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 Pathogenic. Variant got 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 7-105472173-C-T is Pathogenic according to our data. Variant chr7-105472173-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2431797.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PUS7	NM_019042.5	c.1196G>A	p.Trp399Ter	stop_gained	10/16	ENST00000469408.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PUS7	ENST00000469408.6	c.1196G>A	p.Trp399Ter	stop_gained	10/16	1	NM_019042.5	P1
PUS7	ENST00000356362.6	c.1196G>A	p.Trp399Ter	stop_gained	10/16	2		P1
PUS7	ENST00000478208.1	n.16G>A		non_coding_transcript_exon_variant	1/2	3
PUS7	ENST00000481939.5	c.1196G>A	p.Trp399Ter	stop_gained, NMD_transcript_variant	10/17	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual developmental disorder with abnormal behavior, microcephaly, and short stature Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein

Oct 28, 2022

ACMG classification criteria: PVS1 very strong, PM2 moderated -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.65
CADD	Pathogenic	46
DANN	Uncertain	1.0
Eigen	Pathogenic	0.95
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Pathogenic	0.99	D
MutationTaster	Benign	1.0	A;A;A
Vest4		0.57
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: chr7-105112620; COSMIC: COSV62678480;