Variant rs1047978 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.408C>G(p.Asp136Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 1,613,078 control chromosomes in the GnomAD database, including 91,237 homozygotes. In-silico tool predicts 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 0.27 ( 6842 hom., cov: 33)

Exomes 𝑓: 0.34 ( 84395 hom. )

Consequence

C21orf91
NM_001100420.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.915

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=0.0028917491).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.343 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.408C>G	p.Asp136Glu	missense_variant	3/5	ENST00000284881.9	NP_001093890.1
LOC124900465	XR_007067823.1 linkuse as main transcript	n.1605+40049G>C		intron_variant, non_coding_transcript_variant
C21orf91	NM_017447.4 linkuse as main transcript	c.408C>G	p.Asp136Glu	missense_variant	3/5		NP_059143.3
C21orf91	NM_001100421.2 linkuse as main transcript	c.408C>G	p.Asp136Glu	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.408C>G	p.Asp136Glu	missense_variant	3/5	2	NM_001100420.2	ENSP00000284881	P4	Q9NYK6-1
	ENST00000428689.5 linkuse as main transcript	n.71+3280G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.275

AC:

41754

AN:

152010

Hom.:

6843

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0854

Gnomad AMI

AF:

0.471

Gnomad AMR

AF:

0.317

Gnomad ASJ

AF:

0.290

Gnomad EAS

AF:

0.344

Gnomad SAS

AF:

0.302

Gnomad FIN

AF:

0.416

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.347

Gnomad OTH

AF:

0.294

GnomAD3 exomes

AF:

0.325

AC:

80867

AN:

249164

Hom.:

13841

AF XY:

0.328

AC XY:

44356

AN XY:

135186

show subpopulations

Gnomad AFR exome

AF:

0.0748

Gnomad AMR exome

AF:

0.329

Gnomad ASJ exome

AF:

0.314

Gnomad EAS exome

AF:

0.343

Gnomad SAS exome

AF:

0.307

Gnomad FIN exome

AF:

0.399

Gnomad NFE exome

AF:

0.346

Gnomad OTH exome

AF:

0.326

GnomAD4 exome

AF:

0.336

AC:

491408

AN:

1460950

Hom.:

84395

Cov.:

AF XY:

0.336

AC XY:

244356

AN XY:

726816

show subpopulations

Gnomad4 AFR exome

AF:

0.0716

Gnomad4 AMR exome

AF:

0.327

Gnomad4 ASJ exome

AF:

0.301

Gnomad4 EAS exome

AF:

0.364

Gnomad4 SAS exome

AF:

0.306

Gnomad4 FIN exome

AF:

0.398

Gnomad4 NFE exome

AF:

0.345

Gnomad4 OTH exome

AF:

0.323

GnomAD4 genome

AF:

0.274

AC:

41757

AN:

152128

Hom.:

6842

Cov.:

AF XY:

0.278

AC XY:

20672

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.0852

Gnomad4 AMR

AF:

0.317

Gnomad4 ASJ

AF:

0.290

Gnomad4 EAS

AF:

0.345

Gnomad4 SAS

AF:

0.303

Gnomad4 FIN

AF:

0.416

Gnomad4 NFE

AF:

0.347

Gnomad4 OTH

AF:

0.289

Alfa

AF:

0.330

Hom.:

6514

Bravo

AF:

0.260

TwinsUK

AF:

0.341

AC:

1264

ALSPAC

AF:

0.335

AC:

1293

ESP6500AA

AF:

0.0707

AC:

258

ESP6500EA

AF:

0.344

AC:

2813

ExAC

AF:

0.319

AC:

38518

Asia WGS

AF:

0.286

AC:

994

AN:

3478

EpiCase

AF:

0.352

EpiControl

AF:

0.349

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.032

.;.;.;T

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.81

T;T;T;T

MetaRNN

Benign

0.0029

T;T;T;T

MetaSVM

Benign

-0.92

MutationTaster

Benign

0.0096

P;P

PROVEAN

Uncertain

-3.1

D;D;N;N

REVEL

Benign

0.15

Sift

Benign

0.053

T;D;D;D

Sift4G

Uncertain

0.020

D;D;D;.

Vest4

0.25

MutPred

0.34

Gain of disorder (P = 0.1272);Gain of disorder (P = 0.1272);Gain of disorder (P = 0.1272);Gain of disorder (P = 0.1272);

MPC

0.55

ClinPred

0.027

GERP RS

3.4

gMVP

0.35

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