16-1614889-C-T

Variant summary

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

The NM_020825.4(CRAMP1):c.250C>T(p.Arg84Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000085 in 1,177,054 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
• Consequence: CRAMP1 NM_020825.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.914

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]

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	UniProt
CRAMP1	NM_020825.4	c.250C>T	p.Arg84Trp	missense_variant	2/21	ENST00000397412.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRAMP1	ENST00000397412.8	c.250C>T	p.Arg84Trp	missense_variant	2/21	5	NM_020825.4	P1
CRAMP1	ENST00000293925.9	c.250C>T	p.Arg84Trp	missense_variant	1/20	5		P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 8.50e-7 AC: 1 AN: 1177054 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 572226

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: 0.00000103

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

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

Nov 09, 2022

The c.250C>T (p.R84W) 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 250, causing the arginine (R) at amino acid position 84 to be replaced by a tryptophan (W). 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	0.99
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
Cadd	Benign	21
Dann	Uncertain	1.0
DEOGEN2	Pathogenic	0.82	D;D
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.49	N
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.45	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.1	M;M
MutationTaster	Benign	0.87	D;D;D
PrimateAI	Pathogenic	0.95	D
PROVEAN	Uncertain	-4.0	D;D
REVEL	Benign	0.23
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		1.0	D;D
Vest4		0.47
MutPred		0.44		Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);
MVP		0.27
MPC		2.2
ClinPred		1.0	D
GERP RS		-5.9
Varity_R		0.53
gMVP		0.39

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: chr16-1664890;