21-6116503-C-T

Position:

• chr21-6116503-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3 PP5

The NM_001320643.3(LOC102724428):​c.379C>T​(p.Arg127Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 0)
• Consequence: LOC102724428 NM_001320643.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 1.20

Genes affected

LOC102724428 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.808
• PP5: Variant 21-6116503-C-T is Pathogenic according to our data. Variant chr21-6116503-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 433140.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC102724428	NM_001320643.3	c.379C>T	p.Arg127Trp	missense_variant	5/14		NP_001307572.1
LOC102724428	XM_017028208.2	c.379C>T	p.Arg127Trp	missense_variant	5/13		XP_016883697.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Childhood epilepsy with centrotemporal spikes Pathogenic:1

Pathogenic, no assertion criteria provided

case-control

Bioinformatics Core, Luxembourg Center for Systems Biomedicine

Jan 01, 2017

CAADphred>15 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
LIST_S2	Pathogenic	0.99	D
MetaRNN	Pathogenic	0.81	D
Sift4G	Pathogenic	0.0	D
Vest4		0.75
gMVP		0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1555841977; hg19: chr21-44841638;