NM_173629.3:c.6C>G

Variant names:

• chr18-54591288-C-G
• rs776289970
• NM_173629.3:c.6C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173629.3(DYNAP):​c.6C>G​(p.Asp2Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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: 0.0000014 (0 hom.)
• Consequence: DYNAP NM_173629.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.436
• Publications: 0 publications found

Genes affected

DYNAP (HGNC:26808): (dynactin associated protein) Involved in several processes, including activation of protein kinase B activity; cellular response to ergosterol; and positive regulation of cell population proliferation. Located in Golgi apparatus and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12667656).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173629.3. 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
	DYNAP	NM_173629.3	MANE Select	c.6C>G	p.Asp2Glu	missense	Exon 1 of 3	NP_775900.2	A0A3B3IRJ4
	DYNAP	NM_001307955.1		c.93C>G	p.Asp31Glu	missense	Exon 2 of 3	NP_001294884.1	K7EMN5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNAP	ENST00000648945.2	MANE Select	c.6C>G	p.Asp2Glu	missense	Exon 1 of 3	ENSP00000496812.1	A0A3B3IRJ4
	DYNAP	ENST00000321600.1	TSL:2	c.84C>G	p.Asp28Glu	missense	Exon 1 of 3	ENSP00000315265.1	Q8N1N2
	DYNAP	ENST00000585973.1	TSL:3	c.93C>G	p.Asp31Glu	missense	Exon 2 of 3	ENSP00000466577.1	K7EMN5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250598 AF XY: 0.00000738

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460676 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726634

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33394

American (AMR) AF: 0.00 AC: 0 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39638

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86158

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111270

Other (OTH) AF: 0.00 AC: 0 AN: 60326

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

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	0.23
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	11
DANN	Benign	0.67
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.079
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.44
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.098
Sift	Benign	0.17	T
Sift4G	Benign	0.35	T
Polyphen		0.99	D
Vest4		0.20
MutPred		0.29		Gain of helix (P = 0.0425)
MVP		0.14
MPC		0.015
ClinPred		0.17	T
GERP RS		0.67
PromoterAI		-0.0050	Neutral
Varity_R		0.051
gMVP		0.025
Mutation Taster		=95/5	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: rs776289970; hg19: chr18-52258519;