Genetic Variant CRYZL1:p.Thr11Lys (chr21-33631520-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145858.3(CRYZL1):c.32C>A(p.Thr11Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000439 in 1,367,182 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000044 ( 0 hom. )

Consequence

CRYZL1
NM_145858.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.17

Variant links:

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]

CRYZL1 links:

ENSG00000249209 (HGNC:):

ENSG00000249209 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1641101).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRYZL1	NM_145858.3 link	c.32C>A	p.Thr11Lys	missense_variant	Exon 2 of 13	ENST00000381554.8	NP_665857.2	O95825-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CRYZL1	ENST00000381554.8 link	c.32C>A	p.Thr11Lys	missense_variant	Exon 2 of 13	1	NM_145858.3	ENSP00000370966.3	O95825-1
CRYZL1	ENST00000381540.7 link	c.32C>A	p.Thr11Lys	missense_variant	Exon 2 of 13	2		ENSP00000370951.3	A6NND8
ENSG00000249209	ENST00000429238.2 link	c.442-45339C>A		intron_variant	Intron 6 of 7	5		ENSP00000394107.2	H7C0C1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000209

AC:

AN:

191466

Hom.:

AF XY:

0.00

AC XY:

AN XY:

105932

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000322

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:

0.00000439

AC:

AN:

1367182

Hom.:

Cov.:

AF XY:

0.00000147

AC XY:

AN XY:

679500

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000142

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000178

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 06, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.32C>A (p.T11K) alteration is located in exon 2 (coding exon 1) of the CRYZL1 gene. This alteration results from a C to A substitution at nucleotide position 32, causing the threonine (T) at amino acid position 11 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.021

T;T;T;T;T;T;T;T

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.88

D;D;D;D;D;D;D;.

M_CAP

Benign

0.0066

MetaRNN

Benign

0.16

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;.;.;.;.;.;.;.

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.2

N;N;N;N;N;N;N;D

REVEL

Benign

0.071

Sift

Benign

0.037

D;D;T;D;D;D;D;.

Sift4G

Benign

0.26

T;T;T;T;T;.;D;.

Polyphen

0.47

P;.;P;.;P;.;.;.

Vest4

0.30

MutPred

0.41

Gain of ubiquitination at T11 (P = 0.0162);Gain of ubiquitination at T11 (P = 0.0162);Gain of ubiquitination at T11 (P = 0.0162);Gain of ubiquitination at T11 (P = 0.0162);.;Gain of ubiquitination at T11 (P = 0.0162);Gain of ubiquitination at T11 (P = 0.0162);Gain of ubiquitination at T11 (P = 0.0162);

MVP

0.70

MPC

0.27

ClinPred

0.15

GERP RS

5.3

Varity_R

0.076

gMVP

0.29

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over