chr2-36356582-A-C

Variant names:

• chr2-36356582-A-C
• rs201724622
• NM_016441.3:c.290A>C

Variant summary

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

The NM_016441.3(CRIM1):​c.290A>C​(p.Asn97Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,459,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N97S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CRIM1 NM_016441.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.19

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=0.29817462).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRIM1	NM_016441.3	c.290A>C	p.Asn97Thr	missense_variant	Exon 1 of 17	ENST00000280527.7	NP_057525.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRIM1	ENST00000280527.7	c.290A>C	p.Asn97Thr	missense_variant	Exon 1 of 17	1	NM_016441.3	ENSP00000280527.2
CRIM1	ENST00000426856.1	c.140A>C	p.Asn47Thr	missense_variant	Exon 1 of 4	3		ENSP00000407636.1
CRIM1	ENST00000428774.1	c.110A>C	p.Asn37Thr	missense_variant	Exon 1 of 2	3		ENSP00000415706.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000404 AC: 1 AN: 247496 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134760

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000897

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1459778 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726286

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.071	T;.
Eigen	Benign	-0.097
Eigen_PC	Benign	-0.0024
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.83	T;T
M_CAP	Pathogenic	0.86	D
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.2	L;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.62	N;N
REVEL	Benign	0.092
Sift	Uncertain	0.016	D;T
Sift4G	Uncertain	0.014	D;T
Polyphen		0.035	B;.
Vest4		0.32
MutPred		0.34		Gain of phosphorylation at N97 (P = 0.0275);.;
MVP		0.40
MPC		0.84
ClinPred		0.59	D
GERP RS		3.3
Varity_R		0.11
gMVP		0.34

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

LitVar

Other links and lift over

dbSNP: rs201724622; hg19: chr2-36583725;