14-24337267-C-T

Variant names:

• chr14-24337267-C-T
• rs1001294847
• NM_006871.4:c.1094G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_006871.4(RIPK3):​c.1094G>A​(p.Cys365Tyr) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RIPK3 NM_006871.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.65
• Publications: 0 publications found

Genes affected

RIPK3 (HGNC:10021): (receptor interacting serine/threonine kinase 3) The product of this gene is a member of the receptor-interacting protein (RIP) family of serine/threonine protein kinases, and contains a C-terminal domain unique from other RIP family members. The encoded protein is predominantly localized to the cytoplasm, and can undergo nucleocytoplasmic shuttling dependent on novel nuclear localization and export signals. It is a component of the tumor necrosis factor (TNF) receptor-I signaling complex, and can induce apoptosis and weakly activate the NF-kappaB transcription factor. [provided by RefSeq, Jul 2008]

ENSG00000258973 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.025148004).
• BP6: Variant 14-24337267-C-T is Benign according to our data. Variant chr14-24337267-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3154528.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006871.4. 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
	RIPK3	NM_006871.4	MANE Select	c.1094G>A	p.Cys365Tyr	missense	Exon 8 of 10	NP_006862.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIPK3	ENST00000216274.10	TSL:1 MANE Select	c.1094G>A	p.Cys365Tyr	missense	Exon 8 of 10	ENSP00000216274.5	Q9Y572-1
	RIPK3	ENST00000554756.1	TSL:1	n.*436G>A		non_coding_transcript_exon	Exon 8 of 10	ENSP00000452328.1	Q9Y572-3
	RIPK3	ENST00000554756.1	TSL:1	n.*436G>A		3_prime_UTR	Exon 8 of 10	ENSP00000452328.1	Q9Y572-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.061
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.062
DANN	Benign	0.36
DEOGEN2	Benign	0.097	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.019	N
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.025	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.34	N
PhyloP100		-1.6
PrimateAI	Benign	0.29	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Benign	0.12
Sift	Benign	0.45	T
Sift4G	Benign	0.52	T
Polyphen		0.0	B
Vest4		0.16
MutPred		0.23		Gain of catalytic residue at K363 (P = 0.0059)
MVP		0.10
MPC		0.59
ClinPred		0.043	T
GERP RS		-5.1
PromoterAI		0.012	Neutral
Varity_R		0.035
gMVP		0.15
Mutation Taster		=99/1	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: rs1001294847; hg19: chr14-24806473;