11-57646395-C-A

Variant names:

• chr11-57646395-C-A
• rs774747011
• NM_145008.3:c.196G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_145008.3(YPEL4):​c.196G>T​(p.Gly66Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,174 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G66S) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: YPEL4 NM_145008.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91
• Publications: 1 publications found

Genes affected

YPEL4 (HGNC:18328): (yippee like 4) Predicted to enable metal ion binding activity. Predicted to be located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

MIR130AHG (HGNC:55966): (MIR130A host gene)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145008.3. 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
	YPEL4	NM_145008.3	MANE Select	c.196G>T	p.Gly66Cys	missense	Exon 4 of 5	NP_659445.1	Q96NS1
	YPEL4	NM_001363487.2		c.196G>T	p.Gly66Cys	missense	Exon 5 of 6	NP_001350416.1	Q96NS1
	MIR130AHG	NR_186232.1		n.298-3903C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YPEL4	ENST00000300022.8	TSL:1 MANE Select	c.196G>T	p.Gly66Cys	missense	Exon 4 of 5	ENSP00000300022.3	Q96NS1
	YPEL4	ENST00000524592.1	TSL:1	n.816G>T		non_coding_transcript_exon	Exon 3 of 4
	YPEL4	ENST00000528797.5	TSL:1	n.830G>T		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152174 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152174 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74332

African (AFR) AF: 0.00 AC: 0 AN: 41406

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68048

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.32
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.0067	T
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	0.53	N
PhyloP100		7.9
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.55
Sift	Benign	0.18	T
Sift4G	Benign	0.13	T
Polyphen		0.99	D
Vest4		0.91
MutPred		0.32		Loss of sheet (P = 0.1398)
MVP		0.54
MPC		2.3
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.51
gMVP		0.48
Mutation Taster		=51/49	polymorphism

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

Other links and lift over

dbSNP: rs774747011; hg19: chr11-57413868;