14-74763542-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019589.3(YLPM1):c.53C>G(p.Pro18Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000727 in 1,376,336 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P18S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: YLPM1 NM_019589.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.90

Genes affected

YLPM1 (HGNC:17798): (YLP motif containing 1) Enables RNA binding activity. Predicted to be involved in regulation of telomere maintenance. Predicted to act upstream of or within negative regulation of transcription by RNA polymerase II. Located in cytosol and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22970939).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YLPM1	NM_019589.3	c.53C>G	p.Pro18Arg	missense_variant	1/21	ENST00000325680.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YLPM1	ENST00000325680.12	c.53C>G	p.Pro18Arg	missense_variant	1/21	5	NM_019589.3	P2
YLPM1	ENST00000552421.5	c.53C>G	p.Pro18Arg	missense_variant	1/20	5		A2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.27e-7 AC: 1 AN: 1376336 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 678180

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.36e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 13, 2023

The c.53C>G (p.P18R) alteration is located in exon 1 (coding exon 1) of the YLPM1 gene. This alteration results from a C to G substitution at nucleotide position 53, causing the proline (P) at amino acid position 18 to be replaced by an arginine (R). 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	0.30
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
Cadd	Uncertain	25
Dann	Benign	0.92
DEOGEN2	Benign	0.059	T;T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.91	N;N;N
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D;.
Sift4G	Uncertain	0.0020	D;D
Vest4		0.49
MutPred		0.24		Gain of catalytic residue at P20 (P = 5e-04);Gain of catalytic residue at P20 (P = 5e-04);
MVP		0.068
MPC		0.12
ClinPred		0.96	D
GERP RS		4.6
Varity_R		0.55
gMVP		0.22

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-75230245;