Variant 16-1614824-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020825.4(CRAMP1):c.185C>T(p.Pro62Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000244 in 1,271,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

CRAMP1
NM_020825.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.96

Variant links:

Genes affected

CRAMP1 (HGNC:14122): (cramped chromatin regulator homolog 1) Predicted to enable chromatin binding activity. Predicted to be involved in pattern specification process. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

CRAMP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.117598414).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRAMP1	NM_020825.4 linkuse as main transcript	c.185C>T	p.Pro62Leu	missense_variant	2/21	ENST00000397412.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CRAMP1	ENST00000397412.8 linkuse as main transcript	c.185C>T	p.Pro62Leu	missense_variant	2/21	5	NM_020825.4	P1
CRAMP1	ENST00000293925.9 linkuse as main transcript	c.185C>T	p.Pro62Leu	missense_variant	1/20	5		P1
CRAMP1	ENST00000674071.1 linkuse as main transcript			downstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151700

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000442

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000250

AC:

AN:

1119412

Hom.:

Cov.:

AF XY:

0.0000223

AC XY:

AN XY:

538338

show subpopulations

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:

0.0000286

Gnomad4 OTH exome

AF:

0.0000223

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151700

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74080

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000442

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2023

The c.185C>T (p.P62L) alteration is located in exon 1 (coding exon 1) of the CRAMP1 gene. This alteration results from a C to T substitution at nucleotide position 185, causing the proline (P) at amino acid position 62 to be replaced by a leucine (L). 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

0.075

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.34

T;T

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.14

M_CAP

Benign

0.082

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.048

Sift

Benign

0.12

T;T

Sift4G

Uncertain

0.023

D;D

Polyphen

0.0

B;B

Vest4

0.19

MutPred

0.12

Loss of glycosylation at P62 (P = 0.0268);Loss of glycosylation at P62 (P = 0.0268);

MVP

0.043

MPC

1.6

ClinPred

0.097

GERP RS

0.59

Varity_R

0.047

gMVP

0.081

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over