NM_173629.3:c.6C>A

Variant names:

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

Variant summary

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

The NM_173629.3(DYNAP):​c.6C>A​(p.Asp2Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DYNAP NM_173629.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.436

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

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=0.13385287).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNAP	NM_173629.3	c.6C>A	p.Asp2Glu	missense_variant	Exon 1 of 3	ENST00000648945.2	NP_775900.2
DYNAP	NM_001307955.1	c.93C>A	p.Asp31Glu	missense_variant	Exon 2 of 3		NP_001294884.1
DYNAP	XM_011525923.4	c.93C>A	p.Asp31Glu	missense_variant	Exon 3 of 5		XP_011524225.1
DYNAP	XM_017025709.2	c.93C>A	p.Asp31Glu	missense_variant	Exon 3 of 4		XP_016881198.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYNAP	ENST00000648945.2	c.6C>A	p.Asp2Glu	missense_variant	Exon 1 of 3		NM_173629.3	ENSP00000496812.1
DYNAP	ENST00000321600.1	c.84C>A	p.Asp28Glu	missense_variant	Exon 1 of 3	2		ENSP00000315265.1
DYNAP	ENST00000585973.1	c.93C>A	p.Asp31Glu	missense_variant	Exon 2 of 3	3		ENSP00000466577.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	11
DANN	Benign	0.66
DEOGEN2	Benign	0.022	.;.;T
Eigen	Benign	-0.079
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.37	T;T;T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	.;.;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.8	.;.;N
REVEL	Benign	0.098
Sift	Benign	0.17	.;.;T
Sift4G	Benign	0.35	T;.;T
Polyphen		0.99	.;.;D
Vest4		0.20
MutPred		0.29		.;.;Gain of helix (P = 0.0425);
MVP		0.14
MPC		0.015
ClinPred		0.40	T
GERP RS		0.67
Varity_R		0.051
gMVP		0.025

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: chr18-52258519;