rs751508980

Variant names:

• chr8-30179419-A-C
• rs751508980
• NM_006571.4:c.295A>C

Your query was ambiguous. Multiple possible variants found:

• chr8-30179419-A-C
• chr8-30179419-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006571.4(DCTN6):​c.295A>C​(p.Met99Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DCTN6 NM_006571.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.70

Genes affected

DCTN6 (HGNC:16964): (dynactin subunit 6) The protein encoded by this gene contains an RGD (Arg-Gly-Asp) motif in the N-terminal region, which confers adhesive properties to macromolecular proteins like fibronectin. It shares a high degree of sequence similarity with the mouse homolog, which has been suggested to play a role in mitochondrial biogenesis. The exact biological function of this gene is not known. [provided by RefSeq, Jul 2008]

ENSG00000253708 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08991146).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCTN6	NM_006571.4	c.295A>C	p.Met99Leu	missense_variant	Exon 5 of 7	ENST00000221114.8	NP_006562.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCTN6	ENST00000221114.8	c.295A>C	p.Met99Leu	missense_variant	Exon 5 of 7	1	NM_006571.4	ENSP00000221114.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 249876 Hom.: 0 AF XY: 0.00000740 AC XY: 1 AN XY: 135126

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	19
DANN	Benign	0.89
DEOGEN2	Benign	0.099	T;.
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.090	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.90	N;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.18	N;N
REVEL	Benign	0.095
Sift	Benign	1.0	T;T
Sift4G	Benign	0.80	T;T
Polyphen		0.0	B;.
Vest4		0.41
MutPred		0.26		Loss of ubiquitination at K100 (P = 0.044);Loss of ubiquitination at K100 (P = 0.044);
MVP		0.21
MPC		0.18
ClinPred		0.24	T
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.32
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

Other links and lift over

dbSNP: rs751508980; hg19: chr8-30036935;