dbSNP rs1470722706: CYYR1:p.Asp41Tyr (chr21-26566321-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001320768.2(CYYR1):c.121G>T(p.Asp41Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,596 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CYYR1
NM_001320768.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.79

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYYR1	NM_001320768.2 link	c.121G>T	p.Asp41Tyr	missense_variant	Exon 2 of 4	ENST00000652641.2	NP_001307697.2	Q96J86-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CYYR1	ENST00000652641.2 link	c.121G>T	p.Asp41Tyr	missense_variant	Exon 2 of 4		NM_001320768.2	ENSP00000498505.1	Q96J86-2
CYYR1	ENST00000299340.9 link	c.121G>T	p.Asp41Tyr	missense_variant	Exon 2 of 4	1		ENSP00000299340.4	Q96J86-1
CYYR1	ENST00000400043.3 link	c.121G>T	p.Asp41Tyr	missense_variant	Exon 2 of 4	1		ENSP00000382918.3	Q96J86-3
CYYR1-AS1	ENST00000357401.3 link	n.2117-1636C>A		intron_variant	Intron 3 of 3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461596

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727086

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.015

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.066

T;.

Eigen

Benign

0.12

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.85

D;D

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.56

D;D

MetaSVM

Benign

-0.86

MutationAssessor

Benign

0.97

L;L

PrimateAI

Uncertain

0.49

PROVEAN

Pathogenic

-6.9

D;D

REVEL

Benign

0.16

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.029

D;D

Polyphen

0.60

P;.

Vest4

0.78

MutPred

0.44

Gain of catalytic residue at P45 (P = 0.0802);Gain of catalytic residue at P45 (P = 0.0802);

MVP

0.33

MPC

0.13

ClinPred

0.97

GERP RS

3.2

Varity_R

0.71

gMVP

0.62

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over