chr6-106519442-A-C

Position:

• chr6-106519442-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001371242.2(CRYBG1):​c.2234A>C​(p.Lys745Thr) variant causes a missense change. 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: 32)
• Consequence: CRYBG1 NM_001371242.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.79

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30888665).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRYBG1	NM_001371242.2	c.2234A>C	p.Lys745Thr	missense_variant	4/22	ENST00000633556.3
CRYBG1	NM_001624.4	c.1010A>C	p.Lys337Thr	missense_variant	2/20
CRYBG1	XM_047418270.1	c.2312A>C	p.Lys771Thr	missense_variant	5/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRYBG1	ENST00000633556.3	c.2234A>C	p.Lys745Thr	missense_variant	4/22	5	NM_001371242.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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

May 14, 2024

The c.1010A>C (p.K337T) alteration is located in exon 2 (coding exon 2) of the AIM1 gene. This alteration results from a A to C substitution at nucleotide position 1010, causing the lysine (K) at amino acid position 337 to be replaced by a threonine (T). 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	0.12
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.077	.;T
Eigen	Benign	0.066
Eigen_PC	Benign	-0.035
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.77	T;T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.31	T;T
MetaSVM	Benign	-0.33	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.3	.;N
REVEL	Uncertain	0.38
Sift	Uncertain	0.0010	.;D
Sift4G	Benign	0.14	T;D
Polyphen		0.99	.;D
Vest4		0.69
MutPred		0.39		.;Loss of methylation at K337 (P = 0.0028);
MVP		0.70
MPC		0.48
ClinPred		0.95	D
GERP RS		4.3
Varity_R		0.15
gMVP		0.40

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: chr6-106967317;