7-105512131-A-G

Variant names:

• chr7-105512131-A-G
• rs711432
• NM_019042.5:c.-32-3587T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019042.5(PUS7):​c.-32-3587T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (8091 hom., cov: 19)
• Consequence: PUS7 NM_019042.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02
• Publications: 0 publications found

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]

PUS7 Gene-Disease associations (from GenCC):

• intellectual developmental disorder with abnormal behavior, microcephaly, and short stature

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PUS7	NM_019042.5	c.-32-3587T>C		intron_variant	Intron 1 of 15	ENST00000469408.6	NP_061915.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PUS7	ENST00000469408.6	c.-32-3587T>C		intron_variant	Intron 1 of 15	1	NM_019042.5	ENSP00000417402.1
PUS7	ENST00000356362.6	c.-8-3611T>C		intron_variant	Intron 1 of 15	2		ENSP00000348722.2
PUS7	ENST00000481939.5	n.-32-3587T>C		intron_variant	Intron 1 of 16	5		ENSP00000418794.1

Frequencies

GnomAD3 genomes AF: 0.329 AC: 43258 AN: 131566 Hom.: 8062 Cov.: 19

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.319

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.329 AC: 43323 AN: 131662 Hom.: 8091 Cov.: 19 AF XY: 0.328 AC XY: 20705 AN XY: 63066

African (AFR) AF: 0.520 AC: 17944 AN: 34496

American (AMR) AF: 0.298 AC: 3695 AN: 12382

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 922 AN: 3242

East Asian (EAS) AF: 0.186 AC: 814 AN: 4380

South Asian (SAS) AF: 0.351 AC: 1300 AN: 3708

European-Finnish (FIN) AF: 0.243 AC: 1921 AN: 7896

Middle Eastern (MID) AF: 0.209 AC: 56 AN: 268

European-Non Finnish (NFE) AF: 0.254 AC: 15919 AN: 62756

Other (OTH) AF: 0.318 AC: 546 AN: 1718

Alfa AF: 0.294 Hom.: 799

Bravo AF: 0.340

Asia WGS AF: 0.235 AC: 816 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.67
DANN	Benign	0.20
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs711432; hg19: chr7-105152578;