16-1652516-A-T

Position:

• chr16-1652516-A-T

Variant summary

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

The NM_020825.4(CRAMP1):​c.848A>T​(p.Lys283Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CRAMP1 NM_020825.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.14

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]

ENSG00000261732 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRAMP1	NM_020825.4	c.848A>T	p.Lys283Ile	missense_variant	7/21	ENST00000397412.8	NP_065876.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRAMP1	ENST00000397412.8	c.848A>T	p.Lys283Ile	missense_variant	7/21	5	NM_020825.4	ENSP00000380559.2
ENSG00000261732	ENST00000454337.1	n.322A>T		non_coding_transcript_exon_variant	6/23	2		ENSP00000399780.1
CRAMP1	ENST00000293925.9	c.848A>T	p.Lys283Ile	missense_variant	6/20	5		ENSP00000293925.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Mar 24, 2023

The c.848A>T (p.K283I) alteration is located in exon 6 (coding exon 6) of the CRAMP1 gene. This alteration results from a A to T substitution at nucleotide position 848, causing the lysine (K) at amino acid position 283 to be replaced by an isoleucine (I). 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	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.90	D;D
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	.;D
M_CAP	Benign	0.055	D
MetaRNN	Uncertain	0.46	T;T
MetaSVM	Benign	-0.48	T
MutationAssessor	Uncertain	2.6	M;M
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-6.7	D;D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0070	D;D
Polyphen		0.99	D;D
Vest4		0.51
MutPred		0.46		Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MVP		0.33
MPC		2.7
ClinPred		1.0	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.51
gMVP		0.99

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr16-1702517;