6-43306517-C-T

Position:

• chr6-43306517-C-T

Variant summary

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

The NM_206922.3(CRIP3):​c.329G>A​(p.Ser110Asn) variant causes a missense, splice region 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. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CRIP3 NM_206922.3 missense, splice_region
• Scores: Splicing: ADA: 0.3722
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.937

Genes affected

CRIP3 (HGNC:17751): (cysteine rich protein 3) Predicted to enable metal ion binding activity. Predicted to act upstream of or within T cell proliferation. Predicted to be located in cytoplasm. [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=0.1362746).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRIP3	NM_206922.3	c.329G>A	p.Ser110Asn	missense_variant, splice_region_variant	5/8	ENST00000372569.8	NP_996805.2
CRIP3	NM_001366068.1	c.197G>A	p.Gly66Asp	missense_variant, splice_region_variant	4/7		NP_001352997.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRIP3	ENST00000372569.8	c.329G>A	p.Ser110Asn	missense_variant, splice_region_variant	5/8	1	NM_206922.3	ENSP00000361650	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

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

Apr 13, 2023

The c.329G>A (p.S110N) alteration is located in exon 5 (coding exon 5) of the CRIP3 gene. This alteration results from a G to A substitution at nucleotide position 329, causing the serine (S) at amino acid position 110 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	0.090
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.090	.;T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.62	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.7	L;L
MutationTaster	Benign	0.99	N;N
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.25	N;N
REVEL	Benign	0.12
Sift	Benign	0.12	T;T
Sift4G	Benign	0.41	T;T
Polyphen		0.28	B;B
Vest4		0.44
MutPred		0.23		Loss of phosphorylation at S110 (P = 0.0172);Loss of phosphorylation at S110 (P = 0.0172);
MVP		0.73
MPC		0.15
ClinPred		0.26	T
GERP RS		4.1
Varity_R		0.054
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.37
dbscSNV1_RF	Benign	0.36
SpliceAI score (max)		0.060		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: chr6-43274255;