1-152515650-C-A

Position:

• chr1-152515650-C-A

Variant summary

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

The NM_019060.3(CRCT1):​c.267C>A​(p.Asn89Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000141 in 1,416,278 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N89S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: CRCT1 NM_019060.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.580

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=0.07370925).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRCT1	NM_019060.3	c.267C>A	p.Asn89Lys	missense_variant	2/2	ENST00000368790.4
CRCT1	XM_011509656.3	c.267C>A	p.Asn89Lys	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRCT1	ENST00000368790.4	c.267C>A	p.Asn89Lys	missense_variant	2/2	1	NM_019060.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000111 AC: 2 AN: 179914 Hom.: 0 AF XY: 0.0000202 AC XY: 2 AN XY: 99160

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000130

Gnomad OTH exome AF: 0.000211

GnomAD4 exome AF: 0.0000141 AC: 20 AN: 1416278 Hom.: 0 Cov.: 33 AF XY: 0.0000128 AC XY: 9 AN XY: 700790

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000137

Gnomad4 OTH exome AF: 0.0000854

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000852 AC: 1

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

Sep 26, 2022

The c.267C>A (p.N89K) alteration is located in exon 2 (coding exon 1) of the CRCT1 gene. This alteration results from a C to A substitution at nucleotide position 267, causing the asparagine (N) at amino acid position 89 to be replaced by a lysine (K). 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	0.36
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	15
DANN	Benign	0.85
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	N
PROVEAN	Pathogenic	-6.0	D
REVEL	Benign	0.086
Sift4G	Benign	0.31	T
Polyphen		0.0090	B
Vest4		0.25
MutPred		0.21		Gain of MoRF binding (P = 0.0276);
MVP		0.40
MPC		0.37
ClinPred		0.095	T
GERP RS		2.4
Varity_R		0.74
gMVP		0.012

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: rs772557850; hg19: chr1-152488126;