rs779333910

Variant names:

• chr21-33631520-G-T
• rs779333910
• NM_145858.3:c.32C>A

Your query was ambiguous. Multiple possible variants found:

• chr21-33631520-G-T
• chr21-33631520-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.17
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1641101).

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.32C>A	p.Thr11Lys	missense	Exon 2 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.32C>A	p.Thr11Lys	missense	Exon 2 of 13	ENSP00000370966.3	O95825-1
	CRYZL1	ENST00000361534.6	TSL:1	c.104C>A	p.Thr35Lys	missense	Exon 3 of 13	ENSP00000355075.2	A6NHJ8
	CRYZL1	ENST00000381540.7	TSL:2	c.32C>A	p.Thr11Lys	missense	Exon 2 of 13	ENSP00000370951.3	A6NND8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000209 AC: 4 AN: 191466 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000439 AC: 6 AN: 1367182 Hom.: 0 Cov.: 27 AF XY: 0.00000147 AC XY: 1 AN XY: 679500

African (AFR) AF: 0.00 AC: 0 AN: 28352

American (AMR) AF: 0.00 AC: 0 AN: 26228

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23434

East Asian (EAS) AF: 0.000142 AC: 5 AN: 35182

South Asian (SAS) AF: 0.00 AC: 0 AN: 70688

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51208

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5018

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1071034

Other (OTH) AF: 0.0000178 AC: 1 AN: 56038

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.021	T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		5.2
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.071
Sift	Benign	0.037	D
Sift4G	Benign	0.26	T
Polyphen		0.47	P
Vest4		0.30
MutPred		0.41		Gain of ubiquitination at T11 (P = 0.0162)
MVP		0.70
MPC		0.27
ClinPred		0.15	T
GERP RS		5.3
Varity_R		0.076
gMVP		0.29
Mutation Taster		=74/26	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: rs779333910; hg19: chr21-35003826;