5-150711240-G-A

Position:

• chr5-150711240-G-A

Variant summary

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

The NM_016221.4(DCTN4):​c.1292C>T​(p.Pro431Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DCTN4 NM_016221.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.56

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]

ACMG classification

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	Protein	UniProt
DCTN4	NM_016221.4	c.1292C>T	p.Pro431Leu	missense_variant	13/13	ENST00000447998.7	NP_057305.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCTN4	ENST00000447998.7	c.1292C>T	p.Pro431Leu	missense_variant	13/13	1	NM_016221.4	ENSP00000416968.2
DCTN4	ENST00000446090.6	c.1313C>T	p.Pro438Leu	missense_variant	14/14	1		ENSP00000414906.2
DCTN4	ENST00000424236.5	c.1121C>T	p.Pro374Leu	missense_variant	13/13	2		ENSP00000411251.1
DCTN4	ENST00000627368.2	c.*1089C>T		3_prime_UTR_variant	15/15	5		ENSP00000487323.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 21, 2023

The c.1313C>T (p.P438L) alteration is located in exon 14 (coding exon 14) of the DCTN4 gene. This alteration results from a C to T substitution at nucleotide position 1313, causing the proline (P) at amino acid position 438 to be replaced by a leucine (L). 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	0.26
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.051	T;.;.
Eigen	Benign	-0.00098
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.62	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L;.;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.14
Sift	Uncertain	0.0050	D;D;D
Sift4G	Uncertain	0.038	D;D;D
Polyphen		0.0010	B;.;B
Vest4		0.71
MutPred		0.69		Gain of helix (P = 0.0022);.;.;
MVP		0.068
MPC		0.58
ClinPred		0.82	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.25
gMVP		0.48

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-150090802;