Variant 13-20404168-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_015974.3(CRYL1):c.921G>A(p.Met307Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 𝑓 0.000013 ( 0 hom., cov: 32)

Consequence

CRYL1
NM_015974.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.60

Variant links:

Genes affected

CRYL1 (HGNC:18246): (crystallin lambda 1) The uronate cycle functions as an alternative glucose metabolic pathway, accounting for about 5% of daily glucose catabolism. The product of this gene catalyzes the dehydrogenation of L-gulonate into dehydro-L-gulonate in the uronate cycle. The enzyme requires NAD(H) as a coenzyme, and is inhibited by inorganic phosphate. A similar gene in the rabbit is thought to serve a structural role in the lens of the eye. [provided by RefSeq, Jul 2008]

CRYL1 links:

CRYL1 (HGNC:):

CRYL1 links:

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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=0.12786809).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRYL1	NM_015974.3 linkuse as main transcript	c.921G>A	p.Met307Ile	missense_variant	8/8	ENST00000298248.12	NP_057058.2	Q9Y2S2-1V9HWG2
CRYL1	NM_001363647.2 linkuse as main transcript	c.759G>A	p.Met253Ile	missense_variant	7/7		NP_001350576.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRYL1	ENST00000298248.12 linkuse as main transcript	c.921G>A	p.Met307Ile	missense_variant	8/8	1	NM_015974.3	ENSP00000298248.7		Q9Y2S2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 02, 2024

The c.921G>A (p.M307I) alteration is located in exon 8 (coding exon 8) of the CRYL1 gene. This alteration results from a G to A substitution at nucleotide position 921, causing the methionine (M) at amino acid position 307 to be replaced by an isoleucine (I). 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

Uncertain

0.36

BayesDel_addAF

Benign

-0.071

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.072

T;.;.;.

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.88

D;D;.;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.13

T;T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

1.8

L;.;.;.

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.71

N;.;N;.

REVEL

Benign

0.13

Sift

Benign

0.71

T;.;T;.

Sift4G

Benign

0.41

T;.;T;.

Polyphen

0.0

B;.;.;.

Vest4

0.25

MutPred

0.47

Loss of disorder (P = 0.0316);.;.;.;

MVP

0.37

MPC

0.21

ClinPred

0.33

GERP RS

5.8

Varity_R

0.26

gMVP

0.43

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