2-36356620-G-C

Position:

• chr2-36356620-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016441.3(CRIM1):​c.328G>C​(p.Glu110Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CRIM1 NM_016441.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.54

Genes affected

CRIM1 (HGNC:2359): (cysteine rich transmembrane BMP regulator 1) This gene encodes a transmembrane protein containing six cysteine-rich repeat domains and an insulin-like growth factor-binding domain. The encoded protein may play a role in tissue development though interactions with members of the transforming growth factor beta family, such as bone morphogenetic proteins. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33687693).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRIM1	NM_016441.3	c.328G>C	p.Glu110Gln	missense_variant	1/17	ENST00000280527.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRIM1	ENST00000280527.7	c.328G>C	p.Glu110Gln	missense_variant	1/17	1	NM_016441.3	P1
CRIM1	ENST00000426856.1	c.178G>C	p.Glu60Gln	missense_variant	1/4	3
CRIM1	ENST00000428774.1	c.151G>C	p.Glu51Gln	missense_variant	1/2	3

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

Sep 22, 2023

The c.328G>C (p.E110Q) alteration is located in exon 1 (coding exon 1) of the CRIM1 gene. This alteration results from a G to C substitution at nucleotide position 328, causing the glutamic acid (E) at amino acid position 110 to be replaced by a glutamine (Q). 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	0.27
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.049	T;.
Eigen	Benign	0.021
Eigen_PC	Benign	0.062
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.84	T;T
M_CAP	Pathogenic	0.69	D
MetaRNN	Benign	0.34	T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.9	L;.
MutationTaster	Benign	0.97	D
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	0.020	N;N
REVEL	Benign	0.12
Sift	Benign	0.090	T;T
Sift4G	Benign	0.079	T;T
Polyphen		0.50	P;.
Vest4		0.32
MutPred		0.36		Loss of solvent accessibility (P = 0.1744);.;
MVP		0.58
MPC		0.24
ClinPred		0.55	D
GERP RS		2.6
Varity_R		0.10
gMVP		0.52

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: chr2-36583763;