22-21703882-A-G

Position:

• chr22-21703882-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_013313.5(YPEL1):​c.118T>C​(p.Ser40Pro) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: YPEL1 NM_013313.5 missense, splice_region
• Scores: Splicing: ADA: 0.7320
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.16

Genes affected

YPEL1 (HGNC:12845): (yippee like 1) This gene is located in the region associated with DiGeorge syndrome on chromosome 22. The encoded protein localizes to the centrosome and nucleolus and may play a role in the regulation of cell division. [provided by RefSeq, Feb 2015]

YPEL1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.83

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YPEL1	NM_013313.5	c.118T>C	p.Ser40Pro	missense_variant, splice_region_variant	3/5	ENST00000339468.8	NP_037445.1
YPEL1	XM_047441355.1	c.118T>C	p.Ser40Pro	missense_variant, splice_region_variant	3/5		XP_047297311.1
YPEL1	XM_047441356.1	c.118T>C	p.Ser40Pro	missense_variant, splice_region_variant	3/5		XP_047297312.1
YPEL1	NR_130910.2	n.846T>C		non_coding_transcript_exon_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YPEL1	ENST00000339468.8	c.118T>C	p.Ser40Pro	missense_variant, splice_region_variant	3/5	1	NM_013313.5	ENSP00000342832.3
YPEL1	ENST00000672036.2	c.223T>C	p.Ser75Pro	missense_variant, splice_region_variant	2/4			ENSP00000500196.2
YPEL1	ENST00000477675.1	n.813T>C		non_coding_transcript_exon_variant	3/5	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

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 07, 2024

The c.118T>C (p.S40P) alteration is located in exon 3 (coding exon 2) of the YPEL1 gene. This alteration results from a T to C substitution at nucleotide position 118, causing the serine (S) at amino acid position 40 to be replaced by a proline (P). 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	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.40
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.0088	T
MetaRNN	Pathogenic	0.83	D
MetaSVM	Uncertain	0.029	D
MutationAssessor	Pathogenic	2.9	M
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.54
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.078	T
Polyphen		1.0	D
Vest4		0.86
MutPred		0.63		Loss of stability (P = 0.0572);
MVP		0.16
MPC		2.8
ClinPred		0.99	D
GERP RS		4.2
Varity_R		0.61
gMVP		0.78

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.73
dbscSNV1_RF	Benign	0.67
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: chr22-22058171;