4-70249239-G-C

Variant names:

• chr4-70249239-G-C
• rs1048152
• NM_001394997.1:c.329G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001394997.1(CSN3):​c.329G>C​(p.Arg110Pro) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CSN3 NM_001394997.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27
• Publications: 20 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.107072085).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSN3	NM_001394997.1	c.329G>C	p.Arg110Pro	missense_variant	Exon 4 of 5	ENST00000304954.4	NP_001381926.1
CSN3	NM_005212.3	c.329G>C	p.Arg110Pro	missense_variant	Exon 5 of 6		NP_005203.2
CSN3	XM_017007761.2	c.329G>C	p.Arg110Pro	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.329G>C	p.Arg110Pro	missense_variant	Exon 4 of 5	1	NM_001394997.1	ENSP00000304822.3
CSN3	ENST00000689459.1	c.329G>C	p.Arg110Pro	missense_variant	Exon 4 of 5			ENSP00000508633.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 250972 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.025
DANN	Benign	0.57
DEOGEN2	Benign	0.21	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.0	L
PhyloP100		-2.3
PrimateAI	Benign	0.20	T
PROVEAN	Uncertain	-2.6	D
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.025	D
Vest4		0.15
ClinPred		0.087	T
GERP RS		-5.3
Varity_R		0.30
gMVP		0.31
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs1048152; hg19: chr4-71114956;