4-70249077-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/22 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394997.1. 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
	CSN3	NM_001394997.1	MANE Select	c.167C>G	p.Pro56Arg	missense	Exon 4 of 5	NP_001381926.1	P07498
	CSN3	NM_005212.3		c.167C>G	p.Pro56Arg	missense	Exon 5 of 6	NP_005203.2	P07498

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSN3	ENST00000304954.4	TSL:1 MANE Select	c.167C>G	p.Pro56Arg	missense	Exon 4 of 5	ENSP00000304822.3	P07498
	CSN3	ENST00000689459.1		c.167C>G	p.Pro56Arg	missense	Exon 4 of 5	ENSP00000508633.1	P07498

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	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
PhyloP100		-0.77
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
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

hg19: chr4-71114794;