16-1614839-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020825.4(CRAMP1):c.200A>C(p.Gln67Pro) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CRAMP1 NM_020825.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.328

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061252326).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRAMP1	NM_020825.4	c.200A>C	p.Gln67Pro	missense_variant	2/21	ENST00000397412.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRAMP1	ENST00000397412.8	c.200A>C	p.Gln67Pro	missense_variant	2/21	5	NM_020825.4	P1
CRAMP1	ENST00000293925.9	c.200A>C	p.Gln67Pro	missense_variant	1/20	5		P1
CRAMP1	ENST00000674071.1			downstream_gene_variant

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

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

Jul 09, 2021

The c.200A>C (p.Q67P) alteration is located in exon 1 (coding exon 1) of the CRAMP1 gene. This alteration results from a A to C substitution at nucleotide position 200, causing the glutamine (Q) at amino acid position 67 to be replaced by a proline (P). 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	0.051
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
Cadd	Benign	9.8
Dann	Benign	0.36
DEOGEN2	Benign	0.26	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.022	N
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.061	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.60	N;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.014
Sift	Benign	0.27	T;T
Sift4G	Benign	0.28	T;T
Polyphen		0.0	B;B
Vest4		0.13
MutPred		0.15		Gain of glycosylation at Q67 (P = 0.0074);Gain of glycosylation at Q67 (P = 0.0074);
MVP		0.043
MPC		1.2
ClinPred		0.041	T
GERP RS		1.6
Varity_R		0.12
gMVP		0.047

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: chr16-1664840; COSMIC: COSV105876322; COSMIC: COSV105876322;