Variant rs34106261 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006871.4(RIPK3):c.899C>T(p.Thr300Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0486 in 1,609,770 control chromosomes in the GnomAD database, including 2,317 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.063 ( 411 hom., cov: 32)

Exomes 𝑓: 0.047 ( 1906 hom. )

Consequence

RIPK3
NM_006871.4 missense, splice_region

Scores

Splicing: ADA: 0.00005966

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.84

Variant links:

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]

RIPK3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017099977).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIPK3	NM_006871.4 linkuse as main transcript	c.899C>T	p.Thr300Met	missense_variant, splice_region_variant	7/10	ENST00000216274.10	NP_006862.2	Q9Y572-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RIPK3	ENST00000216274.10 linkuse as main transcript	c.899C>T	p.Thr300Met	missense_variant, splice_region_variant	7/10	1	NM_006871.4	ENSP00000216274.5	Q9Y572-1
RIPK3	ENST00000554756.1 linkuse as main transcript	n.*241C>T		splice_region_variant, non_coding_transcript_exon_variant	7/10	1		ENSP00000452328.1	Q9Y572-3
RIPK3	ENST00000554756.1 linkuse as main transcript	n.*241C>T		3_prime_UTR_variant	7/10	1		ENSP00000452328.1	Q9Y572-3

Frequencies

GnomAD3 genomes

AF:

0.0632

AC:

9617

AN:

152150

Hom.:

407

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0502

Gnomad ASJ

AF:

0.109

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0526

Gnomad FIN

AF:

0.0646

Gnomad MID

AF:

0.0701

Gnomad NFE

AF:

0.0448

Gnomad OTH

AF:

0.0699

GnomAD3 exomes

AF:

0.0491

AC:

12231

AN:

249322

Hom.:

386

AF XY:

0.0486

AC XY:

6551

AN XY:

134804

show subpopulations

Gnomad AFR exome

AF:

0.104

Gnomad AMR exome

AF:

0.0300

Gnomad ASJ exome

AF:

0.113

Gnomad EAS exome

AF:

0.0000547

Gnomad SAS exome

AF:

0.0514

Gnomad FIN exome

AF:

0.0647

Gnomad NFE exome

AF:

0.0455

Gnomad OTH exome

AF:

0.0520

GnomAD4 exome

AF:

0.0470

AC:

68575

AN:

1457502

Hom.:

1906

Cov.:

AF XY:

0.0474

AC XY:

34393

AN XY:

725230

show subpopulations

Gnomad4 AFR exome

AF:

0.107

Gnomad4 AMR exome

AF:

0.0328

Gnomad4 ASJ exome

AF:

0.113

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0514

Gnomad4 FIN exome

AF:

0.0657

Gnomad4 NFE exome

AF:

0.0442

Gnomad4 OTH exome

AF:

0.0531

GnomAD4 genome

AF:

0.0633

AC:

9641

AN:

152268

Hom.:

411

Cov.:

AF XY:

0.0646

AC XY:

4811

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.104

Gnomad4 AMR

AF:

0.0501

Gnomad4 ASJ

AF:

0.109

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.0518

Gnomad4 FIN

AF:

0.0646

Gnomad4 NFE

AF:

0.0449

Gnomad4 OTH

AF:

0.0691

Alfa

AF:

0.0484

Hom.:

387

Bravo

AF:

0.0639

TwinsUK

AF:

0.0375

AC:

139

ALSPAC

AF:

0.0436

AC:

168

ESP6500AA

AF:

0.0992

AC:

437

ESP6500EA

AF:

0.0476

AC:

409

ExAC

AF:

0.0497

AC:

6039

Asia WGS

AF:

0.0280

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.0060

DANN

Benign

0.50

DEOGEN2

Benign

0.11

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.0057

MetaRNN

Benign

0.0017

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.46

PrimateAI

Benign

0.21

PROVEAN

Benign

-1.0

REVEL

Benign

0.24

Sift

Benign

0.092

Sift4G

Benign

0.15

Polyphen

0.048

Vest4

0.023

MPC

0.16

ClinPred

0.0097

GERP RS

-9.3

Varity_R

0.018

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000060

dbscSNV1_RF

Benign

0.038

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over