Variant 14-22998879-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021944.4(C14orf93):c.145A>T(p.Thr49Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

C14orf93
NM_021944.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.96

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C14orf93	NM_021944.4 linkuse as main transcript	c.145A>T	p.Thr49Ser	missense_variant	2/7	ENST00000299088.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C14orf93	ENST00000299088.11 linkuse as main transcript	c.145A>T	p.Thr49Ser	missense_variant	2/7	2	NM_021944.4	P1	Q9H972-1
AJUBA-DT	ENST00000556503.5 linkuse as main transcript	n.680-77T>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251366

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461808

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

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.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 14, 2021

The c.145A>T (p.T49S) alteration is located in exon 2 (coding exon 1) of the C14orf93 gene. This alteration results from a A to T substitution at nucleotide position 145, causing the threonine (T) at amino acid position 49 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Uncertain

0.016

BayesDel_noAF

Benign

-0.13

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.022

T;.;T;T;T;T;.;T;.;.;.

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.79

M_CAP

Benign

0.022

MetaRNN

Benign

0.34

T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.69

MutationAssessor

Benign

0.81

L;L;L;L;.;.;.;.;.;.;.

MutationTaster

Benign

0.99

D;D;D;D;D;D

PROVEAN

Benign

-1.9

N;D;N;N;D;D;D;D;D;D;D

REVEL

Uncertain

0.29

Sift

Pathogenic

0.0

D;D;D;D;D;D;D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;.;D;.;.;.;.;.

Polyphen

1.0

D;D;D;D;.;.;.;.;.;.;.

Vest4

0.13

MutPred

0.48

Gain of disorder (P = 0.0489);Gain of disorder (P = 0.0489);Gain of disorder (P = 0.0489);Gain of disorder (P = 0.0489);Gain of disorder (P = 0.0489);Gain of disorder (P = 0.0489);Gain of disorder (P = 0.0489);Gain of disorder (P = 0.0489);Gain of disorder (P = 0.0489);Gain of disorder (P = 0.0489);Gain of disorder (P = 0.0489);

MVP

0.81

MPC

0.96

ClinPred

0.75

GERP RS

5.9

Varity_R

0.43

gMVP

0.36

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