Variant 14-22998491-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_021944.4(C14orf93):c.533A>T(p.Gln178Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0016 in 1,610,512 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 9 hom. )

Consequence

C14orf93
NM_021944.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.11

Variant links:

Genes affected

C14orf93 (HGNC:20162): (chromosome 14 open reading frame 93) Enables RNA binding activity. Predicted to act upstream of or within anatomical structure development; cell differentiation; and positive regulation of gene expression. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

C14orf93 links:

AJUBA-DT (HGNC:55449): (AJUBA divergent transcript)

AJUBA-DT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0071055293).

BP6

Variant 14-22998491-T-A is Benign according to our data. Variant chr14-22998491-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 2644084.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C14orf93	NM_021944.4 linkuse as main transcript	c.533A>T	p.Gln178Leu	missense_variant	2/7	ENST00000299088.11	NP_068763.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C14orf93	ENST00000299088.11 linkuse as main transcript	c.533A>T	p.Gln178Leu	missense_variant	2/7	2	NM_021944.4	ENSP00000299088	P1	Q9H972-1
AJUBA-DT	ENST00000556503.5 linkuse as main transcript	n.680-465T>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00275

AC:

415

AN:

151036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000730

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00377

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0243

Gnomad MID

AF:

0.00340

Gnomad NFE

AF:

0.00199

Gnomad OTH

AF:

0.00145

GnomAD3 exomes

AF:

0.00293

AC:

721

AN:

246396

Hom.:

AF XY:

0.00291

AC XY:

390

AN XY:

134040

show subpopulations

Gnomad AFR exome

AF:

0.0000648

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00282

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0229

Gnomad NFE exome

AF:

0.00166

Gnomad OTH exome

AF:

0.00298

GnomAD4 exome

AF:

0.00148

AC:

2167

AN:

1459354

Hom.:

Cov.:

AF XY:

0.00153

AC XY:

1112

AN XY:

725904

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000450

Gnomad4 ASJ exome

AF:

0.00207

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0208

Gnomad4 NFE exome

AF:

0.000821

Gnomad4 OTH exome

AF:

0.00158

GnomAD4 genome

AF:

0.00275

AC:

415

AN:

151158

Hom.:

Cov.:

AF XY:

0.00353

AC XY:

261

AN XY:

73910

show subpopulations

Gnomad4 AFR

AF:

0.0000728

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00377

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0243

Gnomad4 NFE

AF:

0.00200

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.00199

Hom.:

Bravo

AF:

0.000612

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.00232

AC:

282

EpiCase

AF:

0.00109

EpiControl

AF:

0.000712

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2023

C14orf93: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

T;.;T;T;T;T

Eigen

Benign

0.12

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.68

.;T;.;T;T;T

MetaRNN

Benign

0.0071

T;T;T;T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.81

L;L;L;L;.;.

MutationTaster

Benign

1.0

D;N;N;N;N;N

PROVEAN

Uncertain

-2.6

D;D;D;D;D;D

REVEL

Uncertain

0.32

Sift

Uncertain

0.0070

D;D;D;D;D;D

Sift4G

Uncertain

0.026

D;D;D;D;.;D

Polyphen

0.88

P;P;P;P;.;.

Vest4

0.60

MVP

0.75

MPC

0.95

ClinPred

0.056

GERP RS

5.6

Varity_R

0.12

gMVP

0.39

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over