Genetic Variant CYYR1:p.Glu124Gln (chr21-26468599-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001320768.2(CYYR1):c.370G>C(p.Glu124Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

CYYR1
NM_001320768.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.94

Publications

0 publications found

Variant links:

Genes affected

CYYR1 (HGNC:16274): (cysteine and tyrosine rich 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

CYYR1 links:

CYYR1-AS1 (HGNC:39560): (CYYR1 antisense RNA 1)

CYYR1-AS1 links:

LOC107985474 (HGNC:):

LOC107985474 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10584223).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320768.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CYYR1	NM_001320768.2	MANE Select	c.370G>C	p.Glu124Gln	missense	Exon 4 of 4	NP_001307697.2	Q96J86-2
CYYR1	NM_052954.5		c.367G>C	p.Glu123Gln	missense	Exon 4 of 4	NP_443186.3	Q96J86-1
CYYR1	NR_135472.2		n.883G>C		non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CYYR1	ENST00000652641.2	MANE Select	c.370G>C	p.Glu124Gln	missense	Exon 4 of 4	ENSP00000498505.1	Q96J86-2
CYYR1	ENST00000299340.9	TSL:1	c.367G>C	p.Glu123Gln	missense	Exon 4 of 4	ENSP00000299340.4	Q96J86-1
CYYR1-AS1	ENST00000357401.3	TSL:2	n.187-34983C>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151948

Hom.:

Cov.:

show subpopulations

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.:

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151948

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74212

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41380

American (AMR)

AF:

0.00

AC:

AN:

15236

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.00

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67996

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.013

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.66

M_CAP

Benign

0.0037

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

PhyloP100

1.9

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.6

REVEL

Benign

0.025

Sift

Benign

0.038

Sift4G

Benign

0.17

Polyphen

0.013

Vest4

0.16

MutPred

0.24

Gain of helix (P = 0.1736)

MVP

0.20

MPC

0.052

ClinPred

0.11

GERP RS

2.3

Varity_R

0.10

gMVP

0.46

Mutation Taster

=73/27

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over