14-105479020-C-T

Variant names:

• chr14-105479020-C-T
• rs912899788
• NM_001312.4:c.379C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001312.4(CRIP2):​c.379C>T​(p.Pro127Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000417 in 1,584,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000045 (0 hom.)
• Consequence: CRIP2 NM_001312.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.36
• Publications: 0 publications found

Genes affected

CRIP2 (HGNC:2361): (cysteine rich protein 2) This gene encodes a putative transcription factor with two LIM zinc-binding domains. The encoded protein may participate in the differentiation of smooth muscle tissue. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.829

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001312.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRIP2	NM_001312.4	MANE Select	c.379C>T	p.Pro127Ser	missense	Exon 5 of 8	NP_001303.1	P52943-1
	CRIP2	NM_001270837.2		c.601C>T	p.Pro201Ser	missense	Exon 5 of 8	NP_001257766.1	P52943-2
	CRIP2	NM_001270841.2		c.44-105C>T		intron	N/A	NP_001257770.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRIP2	ENST00000329146.9	TSL:1 MANE Select	c.379C>T	p.Pro127Ser	missense	Exon 5 of 8	ENSP00000328521.5	P52943-1
	CRIP2	ENST00000548309.1	TSL:1	n.1174C>T		non_coding_transcript_exon	Exon 5 of 8
	CRIP2	ENST00000483017.7	TSL:2	c.601C>T	p.Pro201Ser	missense	Exon 5 of 8	ENSP00000426119.2	P52943-2

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151878 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000104 AC: 2 AN: 191960 AF XY: 0.00000947

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000655

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000447 AC: 64 AN: 1432248 Hom.: 0 Cov.: 43 AF XY: 0.0000352 AC XY: 25 AN XY: 710214

African (AFR) AF: 0.00 AC: 0 AN: 32784

American (AMR) AF: 0.0000479 AC: 2 AN: 41742

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25620

East Asian (EAS) AF: 0.00 AC: 0 AN: 38098

South Asian (SAS) AF: 0.00 AC: 0 AN: 82316

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48312

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4194

European-Non Finnish (NFE) AF: 0.0000555 AC: 61 AN: 1100066

Other (OTH) AF: 0.0000169 AC: 1 AN: 59116

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151878 Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2 AN XY: 74176

African (AFR) AF: 0.00 AC: 0 AN: 41346

American (AMR) AF: 0.0000655 AC: 1 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67906

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.0000302

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	D
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Pathogenic	0.72	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Benign	-0.40	T
MutationAssessor	Benign	1.6	L
PhyloP100		5.4
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-6.6	D
REVEL	Uncertain	0.29
Sift	Benign	0.055	T
Sift4G	Uncertain	0.021	D
Polyphen		1.0	D
Vest4		0.70
MutPred		0.44		Gain of catalytic residue at R128 (P = 0.0119)
MVP		0.79
MPC		0.88
ClinPred		0.94	D
GERP RS		3.4
Varity_R		0.30
gMVP		0.59
Mutation Taster		=51/49	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs912899788; hg19: chr14-105945357;