1-1309182-C-T

Variant names:

• chr1-1309182-C-T
• rs764937483
• NM_153339.3:c.232C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_153339.3(PUSL1):​c.232C>T​(p.Leu78Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000719 in 1,389,884 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: PUSL1 NM_153339.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.982
• Publications: 0 publications found

Genes affected

PUSL1 (HGNC:26914): (pseudouridine synthase like 1) Predicted to enable pseudouridine synthase activity. Predicted to be involved in tRNA pseudouridine synthesis. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACAP3 (HGNC:16754): (ArfGAP with coiled-coil, ankyrin repeat and PH domains 3) Predicted to enable GTPase activator activity and metal ion binding activity. Predicted to be involved in regulation of catalytic activity. Predicted to act upstream of or within neuron migration and regulation of neuron projection development. Predicted to be located in growth cone. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP7: Synonymous conserved (PhyloP=-0.982 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153339.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PUSL1	NM_153339.3	MANE Select	c.232C>T	p.Leu78Leu	synonymous	Exon 3 of 8	NP_699170.1	Q8N0Z8-1
	PUSL1	NM_001346116.2		c.232C>T	p.Leu78Leu	synonymous	Exon 3 of 8	NP_001333045.1
	PUSL1	NR_144369.2		n.221C>T		non_coding_transcript_exon	Exon 2 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PUSL1	ENST00000379031.10	TSL:1 MANE Select	c.232C>T	p.Leu78Leu	synonymous	Exon 3 of 8	ENSP00000368318.5	Q8N0Z8-1
	PUSL1	ENST00000467712.1	TSL:5	c.-252C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	ENSP00000462968.1	J3KTG4
	PUSL1	ENST00000892133.1		c.232C>T	p.Leu78Leu	synonymous	Exon 3 of 8	ENSP00000562192.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000686 AC: 1 AN: 145752 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000893

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.19e-7 AC: 1 AN: 1389884 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 687520

African (AFR) AF: 0.00 AC: 0 AN: 31392

American (AMR) AF: 0.00 AC: 0 AN: 36490

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24612

East Asian (EAS) AF: 0.0000275 AC: 1 AN: 36330

South Asian (SAS) AF: 0.00 AC: 0 AN: 79208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34124

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5248

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1084674

Other (OTH) AF: 0.00 AC: 0 AN: 57806

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.2
DANN	Benign	0.89
PhyloP100		-0.98
PromoterAI		0.074	Neutral
Mutation Taster		=100/0	polymorphism

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: rs764937483; hg19: chr1-1244562;