rs1730443151

Variant names:

• chr4-70249419-C-G
• rs1730443151
• NM_001394997.1:c.509C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001394997.1(CSN3):​c.509C>G​(p.Pro170Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,700 control chromosomes in the GnomAD database, with no homozygous occurrence. 15/22 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CSN3 NM_001394997.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.961
• 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.509C>G	p.Pro170Arg	missense	Exon 4 of 5	NP_001381926.1	P07498
	CSN3	NM_005212.3		c.509C>G	p.Pro170Arg	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.509C>G	p.Pro170Arg	missense	Exon 4 of 5	ENSP00000304822.3	P07498
	CSN3	ENST00000689459.1		c.509C>G	p.Pro170Arg	missense	Exon 4 of 5	ENSP00000508633.1	P07498

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461700 Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1 AN XY: 727148

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111930

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.00000378

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	0.25
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.31	T
Eigen	Benign	0.025
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.048	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.96
PrimateAI	Benign	0.31	T
PROVEAN	Pathogenic	-7.5	D
REVEL	Benign	0.18
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.48
MutPred		0.58		Gain of sheet (P = 0.0266)
MVP		0.78
MPC		0.037
ClinPred		0.91	D
GERP RS		3.5
Varity_R		0.38
gMVP		0.51
Mutation Taster		=88/12	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

dbSNP: rs1730443151; hg19: chr4-71115136;