chr21-33631520-G-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_145858.3(CRYZL1):​c.32C>T​(p.Thr11Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000219 in 1,367,182 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. T11K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: CRYZL1 NM_145858.3 missense
• Clinical Significance: Not reported in ClinVar
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29436487).

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>T	p.Thr11Ile	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>T	p.Thr11Ile	missense	Exon 2 of 13	ENSP00000370966.3	O95825-1
	CRYZL1	ENST00000361534.6	TSL:1	c.104C>T	p.Thr35Ile	missense	Exon 3 of 13	ENSP00000355075.2	A6NHJ8
	CRYZL1	ENST00000381540.7	TSL:2	c.32C>T	p.Thr11Ile	missense	Exon 2 of 13	ENSP00000370951.3	A6NND8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000219 AC: 3 AN: 1367182 Hom.: 0 Cov.: 27 AF XY: 0.00000442 AC XY: 3 AN XY: 679500

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

American (AMR) AF: 0.0000381 AC: 1 AN: 26228

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

East Asian (EAS) AF: 0.00 AC: 0 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: 0.00000187 AC: 2 AN: 1071034

Other (OTH) AF: 0.00 AC: 0 AN: 56038

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.023	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.7	L
PhyloP100		5.2
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.042
Sift	Uncertain	0.024	D
Sift4G	Benign	0.18	T
Polyphen		0.86	P
Vest4		0.26
MutPred		0.34		Loss of disorder (P = 0.0289)
MVP		0.76
MPC		0.25
ClinPred		0.83	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.052
gMVP		0.24
Mutation Taster		=75/25	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;