22-21710733-C-T

Position:

• chr22-21710733-C-T

Variant summary

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

The NM_013313.5(YPEL1):​c.12G>A​(p.Met4Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: YPEL1 NM_013313.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.00

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19786295).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YPEL1	NM_013313.5	c.12G>A	p.Met4Ile	missense_variant	2/5	ENST00000339468.8	NP_037445.1
YPEL1	XM_047441355.1	c.12G>A	p.Met4Ile	missense_variant	2/5		XP_047297311.1
YPEL1	XM_047441356.1	c.12G>A	p.Met4Ile	missense_variant	2/5		XP_047297312.1
YPEL1	NR_130910.2	n.356G>A		non_coding_transcript_exon_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YPEL1	ENST00000339468.8	c.12G>A	p.Met4Ile	missense_variant	2/5	1	NM_013313.5	ENSP00000342832.3
YPEL1	ENST00000672036.2	c.117G>A	p.Met39Ile	missense_variant	1/4			ENSP00000500196.2
YPEL1	ENST00000403503.1	c.12G>A	p.Met4Ile	missense_variant	2/3	3		ENSP00000386014.1
YPEL1	ENST00000477675.1	n.323G>A		non_coding_transcript_exon_variant	2/5	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

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

Mar 20, 2024

The c.12G>A (p.M4I) alteration is located in exon 2 (coding exon 1) of the YPEL1 gene. This alteration results from a G to A substitution at nucleotide position 12, causing the methionine (M) at amino acid position 4 to be replaced by an isoleucine (I). 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	0.14
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.019	T;.
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.024
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.68	T;T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.49	N;.
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.84	N;N
REVEL	Benign	0.25
Sift	Benign	0.43	T;T
Sift4G	Benign	0.13	T;T
Polyphen		0.0	B;.
Vest4		0.58
MutPred		0.26		Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);
MVP		0.030
MPC		1.5
ClinPred		0.72	D
GERP RS		4.8
Varity_R		0.28
gMVP		0.45

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: chr22-22065022;