Genetic Variant YLPM1:c.4522-4C>T (chr14-74809376-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_019589.3(YLPM1):c.4522-4C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000806 in 1,600,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000084 ( 0 hom. )

Consequence

YLPM1
NM_019589.3 splice_region, intron

Scores

Splicing: ADA: 0.00007110

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.138

Publications

23 publications found

Variant links:

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]

YLPM1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019589.3. 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
	YLPM1	NM_019589.3	MANE Select	c.4522-4C>T		splice_region intron	N/A	NP_062535.2
	YLPM1	NM_001411052.1		c.2404-4C>T		splice_region intron	N/A	NP_001397981.1	F8VU51

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
YLPM1	ENST00000325680.12	TSL:5 MANE Select	c.4522-4C>T	splice_region intron	N/A	ENSP00000324463.7	P49750-4
YLPM1	ENST00000549293.5	TSL:1	n.3181-4C>T	splice_region intron	N/A	ENSP00000449860.1	H0YIQ2
YLPM1	ENST00000930604.1		c.4516-4C>T	splice_region intron	N/A	ENSP00000600663.1

Frequencies

GnomAD3 genomes

AF:

0.0000461

AC:

AN:

151868

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000485

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:

0.0000736

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000346

AC:

AN:

230924

AF XY:

0.0000400

show subpopulations

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:

0.0000767

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000842

AC:

122

AN:

1448884

Hom.:

Cov.:

AF XY:

0.0000847

AC XY:

AN XY:

719850

show subpopulations

African (AFR)

AF:

0.0000302

AC:

AN:

33070

American (AMR)

AF:

0.00

AC:

AN:

42082

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25646

East Asian (EAS)

AF:

0.00

AC:

AN:

39512

South Asian (SAS)

AF:

0.00

AC:

AN:

84120

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.0000985

AC:

109

AN:

1106178

Other (OTH)

AF:

0.000200

AC:

AN:

59922

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000461

AC:

AN:

151868

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74172

show subpopulations

African (AFR)

AF:

0.0000485

AC:

AN:

41270

American (AMR)

AF:

0.00

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10552

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000736

AC:

AN:

67980

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.561

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000523

Hom.:

2282

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

8.2

(source)

DANN

Benign

0.59

PhyloP100

-0.14

PromoterAI

0.0067

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000071

dbscSNV1_RF

Benign

0.0020

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over