18-54597934-C-G

Variant names:

• chr18-54597934-C-G
• rs760155446
• NM_173629.3:c.344C>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.344C>G​(p.Ser115Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,384 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. S115L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DYNAP NM_173629.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 1 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=0.14341429).

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.344C>G	p.Ser115Trp	missense	Exon 3 of 3	NP_775900.2	A0A3B3IRJ4
	DYNAP	NM_001307955.1		c.266C>G	p.Ser89Trp	missense	Exon 3 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.344C>G	p.Ser115Trp	missense	Exon 3 of 3	ENSP00000496812.1	A0A3B3IRJ4
	DYNAP	ENST00000321600.1	TSL:2	c.422C>G	p.Ser141Trp	missense	Exon 3 of 3	ENSP00000315265.1	Q8N1N2
	DYNAP	ENST00000585973.1	TSL:3	c.266C>G	p.Ser89Trp	missense	Exon 3 of 3	ENSP00000466577.1	K7EMN5

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151990 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000798 AC: 2 AN: 250736 AF XY: 0.0000148

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: 1461394 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726986

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39646

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111756

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151990 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74212

African (AFR) AF: 0.00 AC: 0 AN: 41372

American (AMR) AF: 0.00 AC: 0 AN: 15228

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67990

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000247 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	13
DANN	Benign	0.97
DEOGEN2	Benign	0.077	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		-1.1
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.019
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.015	D
Polyphen		1.0	D
Vest4		0.32
MutPred		0.29		Loss of disorder (P = 0.0055)
MVP		0.030
MPC		0.090
ClinPred		0.92	D
GERP RS		-0.90
Varity_R		0.13
gMVP		0.069

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs760155446; hg19: chr18-52265165;