NM_001394997.1:c.167C>G

Variant names:

• chr4-70249077-C-G
• NM_001394997.1:c.167C>G

Variant summary

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

The NM_001394997.1(CSN3):​c.167C>G​(p.Pro56Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: CSN3 NM_001394997.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.769

Genes affected

CSN3 (HGNC:2446): (casein kappa) Involved in lactation and protein stabilization. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSN3	NM_001394997.1	c.167C>G	p.Pro56Arg	missense_variant	Exon 4 of 5	ENST00000304954.4	NP_001381926.1
CSN3	NM_005212.3	c.167C>G	p.Pro56Arg	missense_variant	Exon 5 of 6		NP_005203.2
CSN3	XM_017007761.2	c.167C>G	p.Pro56Arg	missense_variant	Exon 4 of 5		XP_016863250.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSN3	ENST00000304954.4	c.167C>G	p.Pro56Arg	missense_variant	Exon 4 of 5	1	NM_001394997.1	ENSP00000304822.3
CSN3	ENST00000689459.1	c.167C>G	p.Pro56Arg	missense_variant	Exon 4 of 5			ENSP00000508633.1

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

Dec 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.167C>G (p.P56R) alteration is located in exon 4 (coding exon 3) of the CSN3 gene. This alteration results from a C to G substitution at nucleotide position 167, causing the proline (P) at amino acid position 56 to be replaced by an arginine (R). 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	0.17
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	9.5
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0059	T
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.7	L
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.10
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.034	D
Polyphen		0.99	D
Vest4		0.44
MutPred		0.71		Gain of MoRF binding (P = 0.007);
MVP		0.48
MPC		0.25
ClinPred		0.73	D
GERP RS		-2.5
Varity_R		0.17
gMVP		0.38

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: chr4-71114794;