Variant chr6-106512742-C-A 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_001371242.2(CRYBG1):c.1625C>A(p.Pro542His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,418,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CRYBG1
NM_001371242.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.44

Variant links:

Genes affected

CRYBG1 (HGNC:356): (crystallin beta-gamma domain containing 1) Predicted to enable carbohydrate binding activity. [provided by Alliance of Genome Resources, Apr 2022]

CRYBG1 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=0.120992124).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRYBG1	NM_001371242.2 link	c.1625C>A	p.Pro542His	missense_variant	3/22	ENST00000633556.3	NP_001358171.1
CRYBG1	NM_001624.4 link	c.401C>A	p.Pro134His	missense_variant	1/20		NP_001615.2	Q9Y4K1-1B3KPT0
CRYBG1	XM_047418270.1 link	c.1703C>A	p.Pro568His	missense_variant	4/23		XP_047274226.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRYBG1	ENST00000633556.3 link	c.1625C>A	p.Pro542His	missense_variant	3/22	5	NM_001371242.2	ENSP00000488010.2		A0A0J9YWL0
CRYBG1	ENST00000651520.1 link	c.1466C>A	p.Pro489His	missense_variant	2/2			ENSP00000499126.1		A0A494C1M5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000556

AC:

AN:

179954

Hom.:

AF XY:

0.00

AC XY:

AN XY:

98982

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000715

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:

0.00000141

AC:

AN:

1418210

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

701268

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000530

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.:

Alfa

AF:

0.00000997

Hom.:

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 03, 2024

The c.401C>A (p.P134H) alteration is located in exon 1 (coding exon 1) of the AIM1 gene. This alteration results from a C to A substitution at nucleotide position 401, causing the proline (P) at amino acid position 134 to be replaced by a histidine (H). 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

0.14

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.026

.;T

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.63

T;T

M_CAP

Uncertain

0.093

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.96

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.2

.;N

REVEL

Benign

0.11

Sift

Uncertain

0.0020

.;D

Sift4G

Uncertain

0.0070

D;D

Polyphen

0.79

.;P

Vest4

0.17

MutPred

0.17

.;Loss of catalytic residue at P133 (P = 0.0131);

MVP

0.69

MPC

0.38

ClinPred

0.27

GERP RS

3.3

Varity_R

0.16

gMVP

0.18

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