6-106519844-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001371242.2(CRYBG1):c.2636C>A(p.Pro879His) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CRYBG1 NM_001371242.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.543

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]

ACMG classification

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=0.1927349).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRYBG1	NM_001371242.2	c.2636C>A	p.Pro879His	missense_variant	4/22	ENST00000633556.3
CRYBG1	NM_001624.4	c.1412C>A	p.Pro471His	missense_variant	2/20
CRYBG1	XM_047418270.1	c.2714C>A	p.Pro905His	missense_variant	5/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRYBG1	ENST00000633556.3	c.2636C>A	p.Pro879His	missense_variant	4/22	5	NM_001371242.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

CRYBG1: PM2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
Cadd	Benign	18
Dann	Uncertain	0.99
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.54	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-0.73	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.30	T
Sift4G	Uncertain	0.023	D;D
Polyphen		0.99	.;D
Vest4		0.29
MutPred		0.32		.;Gain of sheet (P = 0.0477);
MVP		0.65
MPC		0.38
ClinPred		0.74	D
GERP RS		4.5
Varity_R		0.28
gMVP		0.12

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

Other links and lift over

dbSNP: rs941622898; hg19: chr6-106967719;