Variant 5-150711228-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016221.4(DCTN4):c.1304T>C(p.Ile435Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

DCTN4
NM_016221.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.502

Variant links:

Genes affected

DCTN4 (HGNC:15518): (dynactin subunit 4) Enables protein N-terminus binding activity. Located in centrosome. [provided by Alliance of Genome Resources, Apr 2022]

DCTN4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.039307415).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCTN4	NM_016221.4 linkuse as main transcript	c.1304T>C	p.Ile435Thr	missense_variant	13/13	ENST00000447998.7	NP_057305.1	Q9UJW0-1Q9NSJ5A0A0S2Z5D4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DCTN4	ENST00000447998.7 linkuse as main transcript	c.1304T>C	p.Ile435Thr	missense_variant	13/13	1	NM_016221.4	ENSP00000416968.2	Q9UJW0-1
DCTN4	ENST00000446090.6 linkuse as main transcript	c.1325T>C	p.Ile442Thr	missense_variant	14/14	1		ENSP00000414906.2	Q9UJW0-3
DCTN4	ENST00000424236.5 linkuse as main transcript	c.1133T>C	p.Ile378Thr	missense_variant	13/13	2		ENSP00000411251.1	Q9UJW0-2
DCTN4	ENST00000627368.2 linkuse as main transcript	c.*1101T>C		3_prime_UTR_variant	15/15	5		ENSP00000487323.1	E5RI97

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1460702

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726638

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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

Nov 09, 2022

The c.1325T>C (p.I442T) alteration is located in exon 14 (coding exon 14) of the DCTN4 gene. This alteration results from a T to C substitution at nucleotide position 1325, causing the isoleucine (I) at amino acid position 442 to be replaced by a threonine (T). 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

0.055

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.022

T;.;.

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.80

T;T;T

M_CAP

Benign

0.0025

MetaRNN

Benign

0.039

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

N;.;.

PrimateAI

Benign

0.42

PROVEAN

Benign

0.79

N;N;N

REVEL

Benign

0.056

Sift

Benign

0.27

T;T;T

Sift4G

Benign

0.58

T;T;T

Polyphen

0.0

B;.;B

Vest4

0.042

MutPred

0.34

Gain of relative solvent accessibility (P = 0.0166);.;.;

MVP

0.043

MPC

0.47

ClinPred

0.41

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.032

gMVP

0.11

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