Variant 10-119104147-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001303111.2(DENND10):c.-225C>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000264 in 1,514,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

DENND10
NM_001303111.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.49

Variant links:

Genes affected

DENND10 (HGNC:31793): (DENN domain containing 10) Enables guanyl-nucleotide exchange factor activity and small GTPase binding activity. Involved in endosome transport via multivesicular body sorting pathway; protein transport; and regulation of early endosome to late endosome transport. Located in late endosome. [provided by Alliance of Genome Resources, Apr 2022]

DENND10 links:

DENND10 (HGNC:):

DENND10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3717631).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DENND10	NM_207009.4 linkuse as main transcript	c.5C>A	p.Ala2Asp	missense_variant	1/9	ENST00000361432.3	NP_996892.1	Q8TCE6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DENND10	ENST00000361432.3 linkuse as main transcript	c.5C>A	p.Ala2Asp	missense_variant	1/9	1	NM_207009.4	ENSP00000354688.2		Q8TCE6-1

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151838

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000220

AC:

AN:

1363038

Hom.:

Cov.:

AF XY:

0.00000149

AC XY:

AN XY:

672874

show subpopulations

Gnomad4 AFR exome

AF:

0.0000355

Gnomad4 AMR exome

AF:

0.00

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:

9.39e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151946

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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 26, 2024

The c.5C>A (p.A2D) alteration is located in exon 1 (coding exon 1) of the FAM45A gene. This alteration results from a C to A substitution at nucleotide position 5, causing the alanine (A) at amino acid position 2 to be replaced by an aspartic acid (D). 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

0.29

BayesDel_addAF

Uncertain

0.050

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0081

.;T

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.23

.;T

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.37

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.34

.;N

PROVEAN

Benign

-0.75

.;N

REVEL

Uncertain

0.33

Sift

Pathogenic

0.0

.;D

Sift4G

Pathogenic

0.0

.;D

Polyphen

0.98

.;D

Vest4

0.35

MutPred

0.22

Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);

MVP

0.51

MPC

0.77

ClinPred

0.63

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.69

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over