rs200900375

Variant names:

• chr21-26566333-A-G
• rs200900375
• NM_001320768.2:c.109T>C

Your query was ambiguous. Multiple possible variants found:

• chr21-26566333-A-G
• chr21-26566333-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001320768.2(CYYR1):​c.109T>C​(p.Ser37Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: CYYR1 NM_001320768.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.941

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

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36158895).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYYR1	NM_001320768.2	c.109T>C	p.Ser37Pro	missense_variant	Exon 2 of 4	ENST00000652641.2	NP_001307697.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYYR1	ENST00000652641.2	c.109T>C	p.Ser37Pro	missense_variant	Exon 2 of 4		NM_001320768.2	ENSP00000498505.1
CYYR1	ENST00000299340.9	c.109T>C	p.Ser37Pro	missense_variant	Exon 2 of 4	1		ENSP00000299340.4
CYYR1	ENST00000400043.3	c.109T>C	p.Ser37Pro	missense_variant	Exon 2 of 4	1		ENSP00000382918.3
CYYR1-AS1	ENST00000357401.3	n.2117-1624A>G		intron_variant	Intron 3 of 3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000159 AC: 4 AN: 251088 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135696

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461582 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727076

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000895

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.034	T;.
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.36	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L;L
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.7	D;D
REVEL	Benign	0.12
Sift	Benign	0.037	D;D
Sift4G	Benign	0.073	T;T
Polyphen		0.86	P;.
Vest4		0.66
MutPred		0.29		Gain of relative solvent accessibility (P = 0.0215);Gain of relative solvent accessibility (P = 0.0215);
MVP		0.32
MPC		0.17
ClinPred		0.41	T
GERP RS		-0.65
Varity_R		0.35
gMVP		0.60

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

LitVar

Other links and lift over

dbSNP: rs200900375; hg19: chr21-27938652;