6-106512786-G-C

Position:

• chr6-106512786-G-C

Variant summary

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

The NM_001371242.2(CRYBG1):​c.1669G>C​(p.Ala557Pro) 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: 33)
• Consequence: CRYBG1 NM_001371242.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.36

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=0.12656066).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRYBG1	NM_001371242.2	c.1669G>C	p.Ala557Pro	missense_variant	3/22	ENST00000633556.3	NP_001358171.1
CRYBG1	NM_001624.4	c.445G>C	p.Ala149Pro	missense_variant	1/20		NP_001615.2
CRYBG1	XM_047418270.1	c.1747G>C	p.Ala583Pro	missense_variant	4/23		XP_047274226.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRYBG1	ENST00000633556.3	c.1669G>C	p.Ala557Pro	missense_variant	3/22	5	NM_001371242.2	ENSP00000488010.2
CRYBG1	ENST00000651520.1	c.1510G>C	p.Ala504Pro	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

Jun 30, 2024

The c.445G>C (p.A149P) alteration is located in exon 1 (coding exon 1) of the AIM1 gene. This alteration results from a G to C substitution at nucleotide position 445, causing the alanine (A) at amino acid position 149 to be replaced by a proline (P). 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	0.082
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	.;T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.58	T;T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.95	T
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.4	.;N
REVEL	Benign	0.13
Sift	Uncertain	0.010	.;D
Sift4G	Benign	0.26	T;D
Polyphen		0.0	.;B
Vest4		0.078
MVP		0.60
MPC		0.11
ClinPred		0.11	T
GERP RS		2.6
Varity_R		0.21
gMVP		0.17

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: chr6-106960661;