Genetic Variant NM_001320768.2:c.109T>A (chr21-26566333-A-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001320768.2(CYYR1):c.109T>A(p.Ser37Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000991 in 1,613,898 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

CYYR1
NM_001320768.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.941

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03248045).

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.109T>A	p.Ser37Thr	missense	Exon 2 of 4	NP_001307697.2	Q96J86-2
CYYR1	NM_052954.5		c.109T>A	p.Ser37Thr	missense	Exon 2 of 4	NP_443186.3	Q96J86-1
CYYR1	NR_135472.2		n.455T>A		non_coding_transcript_exon	Exon 2 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CYYR1	ENST00000652641.2	MANE Select	c.109T>A	p.Ser37Thr	missense	Exon 2 of 4	ENSP00000498505.1	Q96J86-2
CYYR1	ENST00000299340.9	TSL:1	c.109T>A	p.Ser37Thr	missense	Exon 2 of 4	ENSP00000299340.4	Q96J86-1
CYYR1	ENST00000400043.3	TSL:1	c.109T>A	p.Ser37Thr	missense	Exon 2 of 4	ENSP00000382918.3	Q96J86-3

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152198

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:

0.000962

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000757

AC:

AN:

251088

AF XY:

0.0000368

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000979

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461582

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727076

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33470

American (AMR)

AF:

0.00

AC:

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.000252

AC:

AN:

39678

South Asian (SAS)

AF:

0.00

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111842

Other (OTH)

AF:

0.0000166

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152316

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41566

American (AMR)

AF:

0.00

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000964

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000577

AC:

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

0.12

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.015

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.81

M_CAP

Benign

0.0058

MetaRNN

Benign

0.032

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PhyloP100

0.94

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.7

REVEL

Benign

0.049

Sift

Benign

0.040

Sift4G

Benign

0.52

Polyphen

0.26

Vest4

0.44

MVP

0.20

MPC

0.070

ClinPred

0.027

GERP RS

-0.65

Varity_R

0.067

gMVP

0.26

Mutation Taster

=96/4

polymorphism

(source)

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

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over