16-1655936-G-T

Variant summary

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

The NM_020825.4(CRAMP1):c.1179G>T(p.Lys393Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CRAMP1 NM_020825.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.07

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15928009).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRAMP1	NM_020825.4	c.1179G>T	p.Lys393Asn	missense_variant	10/21	ENST00000397412.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRAMP1	ENST00000397412.8	c.1179G>T	p.Lys393Asn	missense_variant	10/21	5	NM_020825.4	P1
CRAMP1	ENST00000293925.9	c.1179G>T	p.Lys393Asn	missense_variant	9/20	5		P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460770 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726684

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Jan 04, 2022

The c.1179G>T (p.K393N) alteration is located in exon 9 (coding exon 9) of the CRAMP1 gene. This alteration results from a G to T substitution at nucleotide position 1179, causing the lysine (K) at amino acid position 393 to be replaced by an asparagine (N). 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	0.23
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
Cadd	Benign	21
Dann	Uncertain	1.0
DEOGEN2	Benign	0.30	T;T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.93	D
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;L
MutationTaster	Benign	0.81	D;D;D;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.026
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.054	T;T
Polyphen		0.76	P;P
Vest4		0.34
MutPred		0.29		Loss of methylation at K393 (P = 0.0071);Loss of methylation at K393 (P = 0.0071);
MVP		0.13
MPC		0.66
ClinPred		0.60	D
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.089
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: chr16-1705937;