chr1-1309210-C-T

Variant names:

• chr1-1309210-C-T
• rs1045224696
• NM_153339.3:c.260C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153339.3(PUSL1):​c.260C>T​(p.Pro87Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000021 in 1,522,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: PUSL1 NM_153339.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.44
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14884752).

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.260C>T	p.Pro87Leu	missense	Exon 3 of 8	NP_699170.1	Q8N0Z8-1
	PUSL1	NM_001346116.2		c.260C>T	p.Pro87Leu	missense	Exon 3 of 8	NP_001333045.1
	PUSL1	NR_144369.2		n.249C>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.260C>T	p.Pro87Leu	missense	Exon 3 of 8	ENSP00000368318.5	Q8N0Z8-1
	PUSL1	ENST00000467712.1	TSL:5	c.-224C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	ENSP00000462968.1	J3KTG4
	PUSL1	ENST00000892133.1		c.260C>T	p.Pro87Leu	missense	Exon 3 of 8	ENSP00000562192.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152224 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000151 AC: 2 AN: 132630 AF XY: 0.0000269

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000340

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000226 AC: 31 AN: 1370558 Hom.: 0 Cov.: 33 AF XY: 0.0000251 AC XY: 17 AN XY: 675970

African (AFR) AF: 0.00 AC: 0 AN: 30878

American (AMR) AF: 0.00 AC: 0 AN: 32900

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22880

East Asian (EAS) AF: 0.00 AC: 0 AN: 36886

South Asian (SAS) AF: 0.00 AC: 0 AN: 75444

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33712

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5260

European-Non Finnish (NFE) AF: 0.0000279 AC: 30 AN: 1075662

Other (OTH) AF: 0.0000176 AC: 1 AN: 56936

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152224 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74366

African (AFR) AF: 0.00 AC: 0 AN: 41448

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.095	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.4
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.042
Sift	Benign	0.052	T
Sift4G	Benign	0.13	T
Polyphen		0.78	P
Vest4		0.17
MutPred		0.34		Loss of disorder (P = 0.0305)
MVP		0.40
MPC		0.15
ClinPred		0.40	T
GERP RS		1.2
PromoterAI		-0.0093	Neutral
Varity_R		0.17
gMVP		0.32
Mutation Taster		=87/13	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: rs1045224696; hg19: chr1-1244590;