14-74763951-T-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_019589.3(YLPM1):c.462T>A(p.Pro154=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 1,128,358 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0087 (4 hom., cov: 17)
  • Exomes 𝑓: 0.011 (72 hom.)
• Consequence: YLPM1 NM_019589.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.27

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 Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 14-74763951-T-A is Benign according to our data. Variant chr14-74763951-T-A is described in ClinVar as [Benign]. Clinvar id is 770997.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.27 with no splicing effect.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0107 (11066/1032828) while in subpopulation MID AF= 0.023 (80/3472). AF 95% confidence interval is 0.019. There are 72 homozygotes in gnomad4_exome. There are 5440 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YLPM1	NM_019589.3	c.462T>A	p.Pro154=	synonymous_variant	1/21	ENST00000325680.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YLPM1	ENST00000325680.12	c.462T>A	p.Pro154=	synonymous_variant	1/21	5	NM_019589.3	P2
YLPM1	ENST00000552421.5	c.462T>A	p.Pro154=	synonymous_variant	1/20	5		A2

Frequencies

GnomAD3 genomes AF: 0.00872 AC: 833 AN: 95478 Hom.: 4 Cov.: 17

Gnomad AFR AF: 0.00368

Gnomad AMI AF: 0.00427

Gnomad AMR AF: 0.0139

Gnomad ASJ AF: 0.0131

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00361

Gnomad FIN AF: 0.00681

Gnomad MID AF: 0.0508

Gnomad NFE AF: 0.0109

Gnomad OTH AF: 0.00883

GnomAD3 exomes AF: 0.00615 AC: 1015 AN: 165022 Hom.: 8 AF XY: 0.00654 AC XY: 580 AN XY: 88702

Gnomad AFR exome AF: 0.00238

Gnomad AMR exome AF: 0.00422

Gnomad ASJ exome AF: 0.0108

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00132

Gnomad FIN exome AF: 0.00240

Gnomad NFE exome AF: 0.00958

Gnomad OTH exome AF: 0.00713

GnomAD4 exome AF: 0.0107 AC: 11066 AN: 1032828 Hom.: 72 Cov.: 33 AF XY: 0.0108 AC XY: 5440 AN XY: 503500

Gnomad4 AFR exome AF: 0.00256

Gnomad4 AMR exome AF: 0.00535

Gnomad4 ASJ exome AF: 0.0197

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00226

Gnomad4 FIN exome AF: 0.00481

Gnomad4 NFE exome AF: 0.0119

Gnomad4 OTH exome AF: 0.0109

GnomAD4 genome AF: 0.00870 AC: 831 AN: 95530 Hom.: 4 Cov.: 17 AF XY: 0.00856 AC XY: 375 AN XY: 43828

Gnomad4 AFR AF: 0.00363

Gnomad4 AMR AF: 0.0139

Gnomad4 ASJ AF: 0.0131

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00362

Gnomad4 FIN AF: 0.00681

Gnomad4 NFE AF: 0.0109

Gnomad4 OTH AF: 0.00881

Alfa AF: 0.00672 Hom.: 3

Bravo AF: 0.00593

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 13, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.3
Dann	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

LitVar

Other links and lift over

dbSNP: rs139231018; hg19: chr14-75230654;