rs138481821

Variant names:

• chr8-30180565-A-G
• rs138481821
• NM_006571.4:c.409A>G

Your query was ambiguous. Multiple possible variants found:

• chr8-30180565-A-G
• chr8-30180565-A-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006571.4(DCTN6):​c.409A>G​(p.Ile137Val) variant causes a missense change. The variant allele was found at a frequency of 0.000144 in 1,614,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00073 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000083 (0 hom.)
• Consequence: DCTN6 NM_006571.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.64
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.018933654).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006571.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCTN6	NM_006571.4	MANE Select	c.409A>G	p.Ile137Val	missense	Exon 6 of 7	NP_006562.1	O00399

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCTN6	ENST00000221114.8	TSL:1 MANE Select	c.409A>G	p.Ile137Val	missense	Exon 6 of 7	ENSP00000221114.3	O00399
	DCTN6	ENST00000882954.1		c.409A>G	p.Ile137Val	missense	Exon 6 of 7	ENSP00000553013.1
	DCTN6	ENST00000520829.5	TSL:2	c.409A>G	p.Ile137Val	missense	Exon 6 of 6	ENSP00000431017.1	E5RK00

Frequencies

GnomAD3 genomes AF: 0.000716 AC: 109 AN: 152172 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00253

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

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: 0.000479

GnomAD2 exomes AF: 0.000155 AC: 39 AN: 251262 AF XY: 0.0000884

Gnomad AFR exome AF: 0.00209

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000828 AC: 121 AN: 1461804 Hom.: 0 Cov.: 30 AF XY: 0.0000605 AC XY: 44 AN XY: 727210

African (AFR) AF: 0.00287 AC: 96 AN: 33478

American (AMR) AF: 0.000157 AC: 7 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5752

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111980

Other (OTH) AF: 0.000215 AC: 13 AN: 60392

GnomAD4 genome AF: 0.000729 AC: 111 AN: 152290 Hom.: 0 Cov.: 32 AF XY: 0.000698 AC XY: 52 AN XY: 74464

African (AFR) AF: 0.00257 AC: 107 AN: 41564

American (AMR) AF: 0.000196 AC: 3 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.000273 Hom.: 1

Bravo AF: 0.000744

ESP6500AA AF: 0.00159 AC: 7

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000214 AC: 26

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.098
Eigen_PC	Benign	0.081
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.86	L
PhyloP100		5.6
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.24
Sift	Benign	0.13	T
Sift4G	Benign	0.29	T
Polyphen		0.0010	B
Vest4		0.39
MVP		0.31
MPC		0.16
ClinPred		0.069	T
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.26
Mutation Taster		=73/27	polymorphism

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

Other links and lift over

dbSNP: rs138481821; hg19: chr8-30038081;