rs3746891

Variant names:

• chr21-41741197-T-A
• rs3746891
• NM_020639.3:c.1996A>T

Your query was ambiguous. Multiple possible variants found:

• chr21-41741197-T-A
• chr21-41741197-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020639.3(RIPK4):​c.1996A>T​(p.Met666Leu) 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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M666V) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 36)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RIPK4 NM_020639.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.675

Genes affected

RIPK4 (HGNC:496): (receptor interacting serine/threonine kinase 4) The protein encoded by this gene is a serine/threonine protein kinase that interacts with protein kinase C-delta. The encoded protein can also activate NFkappaB and is required for keratinocyte differentiation. This kinase undergoes autophosphorylation. [provided by RefSeq, Jul 2008]

ENSG00000236883 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.032879263).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPK4	NM_020639.3	c.1996A>T	p.Met666Leu	missense_variant	Exon 8 of 8	ENST00000332512.8	NP_065690.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIPK4	ENST00000332512.8	c.1996A>T	p.Met666Leu	missense_variant	Exon 8 of 8	1	NM_020639.3	ENSP00000332454.3
RIPK4	ENST00000352483.3	c.2140A>T	p.Met714Leu	missense_variant	Exon 9 of 9	5		ENSP00000330161.2
ENSG00000236883	ENST00000423276.1	n.350T>A		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes Cov.: 36

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1457930 Hom.: 0 Cov.: 89 AF XY: 0.00 AC XY: 0 AN XY: 724984

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 36

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	4.6
DANN	Benign	0.73
DEOGEN2	Benign	0.042	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.11	T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.033	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.41	N;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.44	N;N
REVEL	Benign	0.047
Sift	Benign	0.74	T;T
Sift4G	Benign	0.64	T;T
Polyphen		0.0	.;B
Vest4		0.057
MutPred		0.46		.;Loss of phosphorylation at Y671 (P = 0.1469);
MVP		0.40
MPC		0.40
ClinPred		0.042	T
GERP RS		-0.094
Varity_R		0.057
gMVP		0.11

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

Publications

LitVar

Other links and lift over

dbSNP: rs3746891; hg19: chr21-43161357;