chr6-43308788-C-G

Position:

• chr6-43308788-C-G

Variant summary

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

The NM_206922.3(CRIP3):​c.5G>C​(p.Ser2Thr) variant causes a missense 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. 14/21 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: CRIP3 NM_206922.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.590

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]

ZNF318 (HGNC:13578): (zinc finger protein 318) Predicted to enable protein heterodimerization activity and protein homodimerization activity. Predicted to be involved in negative regulation of transcription, DNA-templated and positive regulation of transcription, DNA-templated. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=0.27942938).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRIP3	NM_206922.3	c.5G>C	p.Ser2Thr	missense_variant	1/8	ENST00000372569.8	NP_996805.2
CRIP3	NM_001366068.1	c.5G>C	p.Ser2Thr	missense_variant	1/7		NP_001352997.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRIP3	ENST00000372569.8	c.5G>C	p.Ser2Thr	missense_variant	1/8	1	NM_206922.3	ENSP00000361650	P1
CRIP3	ENST00000274990.4	c.5G>C	p.Ser2Thr	missense_variant	1/7	1		ENSP00000274990
ZNF318	ENST00000607252.5	n.328-379G>C		intron_variant, non_coding_transcript_variant		1
CRIP3	ENST00000485819.1	n.1G>C		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Jul 06, 2021

The c.5G>C (p.S2T) alteration is located in exon 1 (coding exon 1) of the CRIP3 gene. This alteration results from a G to C substitution at nucleotide position 5, causing the serine (S) at amino acid position 2 to be replaced by a threonine (T). 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	0.13
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	.;T
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.61	T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.28	T;T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	0.36	N;N
MutationTaster	Benign	0.59	N;N
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.37	N;N
REVEL	Benign	0.11
Sift	Benign	0.23	T;T
Sift4G	Benign	0.52	T;T
Polyphen		0.035	B;P
Vest4		0.55
MutPred		0.28		Gain of glycosylation at S2 (P = 0.0967);Gain of glycosylation at S2 (P = 0.0967);
MVP		0.81
MPC		0.11
ClinPred		0.90	D
GERP RS		5.1
Varity_R		0.27
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr6-43276526;