Variant rs2824495 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001100420.2(C21orf91):c.345C>G(p.Asn115Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 1,612,780 control chromosomes in the GnomAD database, including 38,576 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.21 ( 3487 hom., cov: 32)

Exomes 𝑓: 0.22 ( 35089 hom. )

Consequence

C21orf91
NM_001100420.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.770

Variant links:

Genes affected

C21orf91 (HGNC:16459): (chromosome 21 open reading frame 91) Predicted to be involved in cerebral cortex neuron differentiation and positive regulation of dendritic spine development. [provided by Alliance of Genome Resources, Apr 2022]

C21orf91 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021314323).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
C21orf91	NM_001100420.2 linkuse as main transcript	c.345C>G	p.Asn115Lys	missense_variant	3/5	ENST00000284881.9	NP_001093890.1
LOC124900465	XR_007067823.1 linkuse as main transcript	n.1605+40112G>C		intron_variant, non_coding_transcript_variant
C21orf91	NM_017447.4 linkuse as main transcript	c.345C>G	p.Asn115Lys	missense_variant	3/5		NP_059143.3
C21orf91	NM_001100421.2 linkuse as main transcript	c.345C>G	p.Asn115Lys	missense_variant	3/4		NP_001093891.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C21orf91	ENST00000284881.9 linkuse as main transcript	c.345C>G	p.Asn115Lys	missense_variant	3/5	2	NM_001100420.2	ENSP00000284881	P4	Q9NYK6-1
	ENST00000428689.5 linkuse as main transcript	n.71+3343G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.208

AC:

31618

AN:

151978

Hom.:

3483

Cov.:

show subpopulations

Gnomad AFR

AF:

0.207

Gnomad AMI

AF:

0.196

Gnomad AMR

AF:

0.244

Gnomad ASJ

AF:

0.155

Gnomad EAS

AF:

0.399

Gnomad SAS

AF:

0.193

Gnomad FIN

AF:

0.127

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.204

Gnomad OTH

AF:

0.173

GnomAD3 exomes

AF:

0.217

AC:

54042

AN:

249026

Hom.:

6466

AF XY:

0.211

AC XY:

28559

AN XY:

135134

show subpopulations

Gnomad AFR exome

AF:

0.206

Gnomad AMR exome

AF:

0.266

Gnomad ASJ exome

AF:

0.152

Gnomad EAS exome

AF:

0.400

Gnomad SAS exome

AF:

0.185

Gnomad FIN exome

AF:

0.130

Gnomad NFE exome

AF:

0.206

Gnomad OTH exome

AF:

0.206

GnomAD4 exome

AF:

0.215

AC:

314156

AN:

1460684

Hom.:

35089

Cov.:

AF XY:

0.213

AC XY:

154523

AN XY:

726766

show subpopulations

Gnomad4 AFR exome

AF:

0.201

Gnomad4 AMR exome

AF:

0.259

Gnomad4 ASJ exome

AF:

0.155

Gnomad4 EAS exome

AF:

0.388

Gnomad4 SAS exome

AF:

0.187

Gnomad4 FIN exome

AF:

0.138

Gnomad4 NFE exome

AF:

0.215

Gnomad4 OTH exome

AF:

0.214

GnomAD4 genome

AF:

0.208

AC:

31630

AN:

152096

Hom.:

3487

Cov.:

AF XY:

0.206

AC XY:

15327

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.207

Gnomad4 AMR

AF:

0.244

Gnomad4 ASJ

AF:

0.155

Gnomad4 EAS

AF:

0.399

Gnomad4 SAS

AF:

0.193

Gnomad4 FIN

AF:

0.127

Gnomad4 NFE

AF:

0.204

Gnomad4 OTH

AF:

0.170

Alfa

AF:

0.164

Hom.:

745

Bravo

AF:

0.219

TwinsUK

AF:

0.220

AC:

816

ALSPAC

AF:

0.219

AC:

845

ESP6500AA

AF:

0.214

AC:

777

ESP6500EA

AF:

0.202

AC:

1655

ExAC

AF:

0.217

AC:

26168

Asia WGS

AF:

0.275

AC:

955

AN:

3476

EpiCase

AF:

0.196

EpiControl

AF:

0.207

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

5.6

DANN

Benign

0.77

DEOGEN2

Benign

0.0047

.;.;.;T

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.17

LIST_S2

Uncertain

0.86

D;D;D;D

MetaRNN

Benign

0.0021

T;T;T;T

MetaSVM

Benign

-0.91

MutationTaster

Benign

1.0

P;P

PROVEAN

Benign

-0.76

N;N;N;N

REVEL

Benign

0.035

Sift

Benign

0.66

T;T;T;T

Sift4G

Benign

0.32

T;T;T;.

Vest4

0.035

MutPred

0.23

Gain of ubiquitination at N115 (P = 0.006);Gain of ubiquitination at N115 (P = 0.006);Gain of ubiquitination at N115 (P = 0.006);Gain of ubiquitination at N115 (P = 0.006);

MPC

0.17

ClinPred

0.0025

GERP RS

0.94

gMVP

0.076

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

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