chr21-33599171-C-T

Variant names:

• chr21-33599171-C-T
• rs1569082909
• NM_145858.3:c.655G>A

Variant summary

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

The NM_145858.3(CRYZL1):​c.655G>A​(p.Asp219Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. D219Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CRYZL1 NM_145858.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.21
• Publications: 0 publications found

Genes affected

CRYZL1 (HGNC:2420): (crystallin zeta like 1) This gene encodes a protein that has sequence similarity to zeta crystallin, also known as quinone oxidoreductase. This zeta crystallin-like protein also contains an NAD(P)H binding site. Alternatively spliced transcript variants have been observed but their full-length nature has not been completely determined. [provided by RefSeq, Jul 2008]

ENSG00000249209 (HGNC:):

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_145858.3. 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
	CRYZL1	NM_145858.3	MANE Select	c.655G>A	p.Asp219Asn	missense	Exon 9 of 13	NP_665857.2	O95825-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRYZL1	ENST00000381554.8	TSL:1 MANE Select	c.655G>A	p.Asp219Asn	missense	Exon 9 of 13	ENSP00000370966.3	O95825-1
	CRYZL1	ENST00000361534.6	TSL:1	c.727G>A	p.Asp243Asn	missense	Exon 10 of 13	ENSP00000355075.2	A6NHJ8
	CRYZL1	ENST00000381540.7	TSL:2	c.655G>A	p.Asp219Asn	missense	Exon 9 of 13	ENSP00000370951.3	A6NND8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-0.39	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		6.2
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.33
Sift	Benign	0.097	T
Sift4G	Uncertain	0.038	D
Polyphen		0.97	D
Vest4		0.98
MutPred		0.81		Gain of sheet (P = 0.0827)
MVP		0.55
MPC		0.80
ClinPred		0.97	D
GERP RS		5.8
Varity_R		0.49
gMVP		0.76
Mutation Taster		=59/41	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: rs1569082909; hg19: chr21-34971477; COSMIC: COSV51679268; COSMIC: COSV51679268;