chr1-152515504-G-C

Position:

• chr1-152515504-G-C

Variant summary

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

The NM_019060.3(CRCT1):​c.121G>C​(p.Gly41Arg) 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. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: CRCT1 NM_019060.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.291

Genes affected

CRCT1 (HGNC:29875): (cysteine rich C-terminal 1)

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=0.14568746).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRCT1	NM_019060.3	c.121G>C	p.Gly41Arg	missense_variant	2/2	ENST00000368790.4
CRCT1	XM_011509656.3	c.121G>C	p.Gly41Arg	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRCT1	ENST00000368790.4	c.121G>C	p.Gly41Arg	missense_variant	2/2	1	NM_019060.3	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 53

GnomAD4 genome Cov.: 34

Bravo AF: 0.00000378

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 02, 2023

The c.121G>C (p.G41R) alteration is located in exon 2 (coding exon 1) of the CRCT1 gene. This alteration results from a G to C substitution at nucleotide position 121, causing the glycine (G) at amino acid position 41 to be replaced by an arginine (R). 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	Uncertain	0.35
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	17
DANN	Benign	0.73
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N
PROVEAN	Pathogenic	-6.4	D
REVEL	Benign	0.12
Sift4G	Benign	0.073	T
Polyphen		0.77	P
Vest4		0.30
MutPred		0.14		Loss of catalytic residue at G41 (P = 0.0423);
MVP		0.29
MPC		0.38
ClinPred		0.36	T
GERP RS		-0.40
Varity_R		0.51
gMVP		0.017

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1658724497; hg19: chr1-152487980;