Genetic Variant CRYBG2:p.Gly1636Ser (chr1-26322048-C-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_001039775.4(CRYBG2):c.4906G>A(p.Gly1636Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CRYBG2
NM_001039775.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.456

Variant links:

Genes affected

CRYBG2 (HGNC:17295): (crystallin beta-gamma domain containing 2) Predicted to enable carbohydrate binding activity. [provided by Alliance of Genome Resources, Apr 2022]

CRYBG2 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=0.14386058).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRYBG2	NM_001039775.4 link	c.4906G>A	p.Gly1636Ser	missense_variant	Exon 20 of 20	ENST00000308182.10	NP_001034864.2	Q8N1P7Q9NWG5
CRYBG2	XM_011541673.3 link	c.5077G>A	p.Gly1693Ser	missense_variant	Exon 20 of 20		XP_011539975.1
CRYBG2	XM_005245918.3 link	c.4906G>A	p.Gly1636Ser	missense_variant	Exon 20 of 20		XP_005245975.1	Q8N1P7
CRYBG2	XM_011541672.2 link	c.4870G>A	p.Gly1624Ser	missense_variant	Exon 19 of 19		XP_011539974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CRYBG2	ENST00000308182.10 link	c.4906G>A	p.Gly1636Ser	missense_variant	Exon 20 of 20	5	NM_001039775.4	ENSP00000310435.6	Q8N1P7
CRYBG2	ENST00000475866.3 link	c.5878G>A	p.Gly1960Ser	missense_variant	Exon 22 of 22	4		ENSP00000428746.2	E7ET48
CRYBG2	ENST00000374208.1 link	n.384G>A		non_coding_transcript_exon_variant	Exon 4 of 4	5
CRYBG2	ENST00000374211.5 link	n.520G>A		non_coding_transcript_exon_variant	Exon 4 of 4	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1454324

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721686

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 09, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4906G>A (p.G1636S) alteration is located in exon 20 (coding exon 19) of the AIM1L gene. This alteration results from a G to A substitution at nucleotide position 4906, causing the glycine (G) at amino acid position 1636 to be replaced by a serine (S). 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

0.21

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.82

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.0036

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.41

REVEL

Benign

0.050

Sift4G

Benign

0.66

.;T

Vest4

0.15

MVP

0.25

ClinPred

0.71

GERP RS

3.4

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over