chr6-106512477-C-G

Position:

• chr6-106512477-C-G

Variant summary

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

The NM_001371242.2(CRYBG1):​c.1360C>G​(p.Pro454Ala) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CRYBG1 NM_001371242.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.84

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=0.21305788).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRYBG1	NM_001371242.2	c.1360C>G	p.Pro454Ala	missense_variant	3/22	ENST00000633556.3	NP_001358171.1
CRYBG1	NM_001624.4	c.136C>G	p.Pro46Ala	missense_variant	1/20		NP_001615.2
CRYBG1	XM_047418270.1	c.1438C>G	p.Pro480Ala	missense_variant	4/23		XP_047274226.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRYBG1	ENST00000633556.3	c.1360C>G	p.Pro454Ala	missense_variant	3/22	5	NM_001371242.2	ENSP00000488010.2
CRYBG1	ENST00000651520.1	c.1201C>G	p.Pro401Ala	missense_variant	2/2			ENSP00000499126.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 27, 2024

The c.136C>G (p.P46A) alteration is located in exon 1 (coding exon 1) of the AIM1 gene. This alteration results from a C to G substitution at nucleotide position 136, causing the proline (P) at amino acid position 46 to be replaced by an alanine (A). 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	0.071
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	.;T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.77	T;T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.31	T
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.3	.;N
REVEL	Benign	0.27
Sift	Benign	0.076	.;T
Sift4G	Benign	0.17	T;T
Polyphen		1.0	.;D
Vest4		0.32
MutPred		0.16		.;Gain of helix (P = 0.0034);
MVP		0.79
MPC		0.18
ClinPred		0.70	D
GERP RS		4.2
Varity_R		0.10
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-106960352;