Variant 6-106512561-G-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_001371242.2(CRYBG1):c.1444G>T(p.Ala482Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000344 in 1,454,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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: 0.0000034 ( 0 hom. )

Consequence

CRYBG1
NM_001371242.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.958

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:

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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=0.14200982).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CRYBG1	NM_001371242.2 linkuse as main transcript	c.1444G>T	p.Ala482Ser	missense_variant	3/22	ENST00000633556.3
CRYBG1	NM_001624.4 linkuse as main transcript	c.220G>T	p.Ala74Ser	missense_variant	1/20
CRYBG1	XM_047418270.1 linkuse as main transcript	c.1522G>T	p.Ala508Ser	missense_variant	4/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRYBG1	ENST00000633556.3 linkuse as main transcript	c.1444G>T	p.Ala482Ser	missense_variant	3/22	5	NM_001371242.2	P1
CRYBG1	ENST00000651520.1 linkuse as main transcript	c.1285G>T	p.Ala429Ser	missense_variant	2/2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000435

AC:

AN:

229790

Hom.:

AF XY:

0.00

AC XY:

AN XY:

126380

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000299

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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:

0.00000344

AC:

AN:

1454974

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

723222

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000907

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:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000830

AC:

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

Oct 20, 2023

The c.220G>T (p.A74S) alteration is located in exon 1 (coding exon 1) of the AIM1 gene. This alteration results from a G to T substitution at nucleotide position 220, causing the alanine (A) at amino acid position 74 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

0.088

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0062

.;T

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.071

LIST_S2

Benign

0.60

T;T

M_CAP

Benign

0.037

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-0.88

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.55

.;N

REVEL

Benign

0.17

Sift

Uncertain

0.0080

.;D

Sift4G

Benign

0.067

T;T

Polyphen

0.99

.;D

Vest4

0.062

MutPred

0.16

.;Gain of phosphorylation at A74 (P = 0.0046);

MVP

0.76

MPC

0.079

ClinPred

0.25

GERP RS

1.9

Varity_R

0.11

gMVP

0.11

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