18-54597889-C-T

Variant names:

• chr18-54597889-C-T
• NM_173629.3:c.299C>T

Variant summary

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

The NM_173629.3(DYNAP):​c.299C>T​(p.Thr100Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,380 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. T100R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DYNAP NM_173629.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.88

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNAP	NM_173629.3	c.299C>T	p.Thr100Ile	missense_variant	Exon 3 of 3	ENST00000648945.2	NP_775900.2
DYNAP	NM_001307955.1	c.221C>T	p.Thr74Ile	missense_variant	Exon 3 of 3		NP_001294884.1
DYNAP	XM_011525923.4	c.386C>T	p.Thr129Ile	missense_variant	Exon 5 of 5		XP_011524225.1
DYNAP	XM_017025709.2	c.221C>T	p.Thr74Ile	missense_variant	Exon 4 of 4		XP_016881198.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYNAP	ENST00000648945.2	c.299C>T	p.Thr100Ile	missense_variant	Exon 3 of 3		NM_173629.3	ENSP00000496812.1
DYNAP	ENST00000321600.1	c.377C>T	p.Thr126Ile	missense_variant	Exon 3 of 3	2		ENSP00000315265.1
DYNAP	ENST00000585973.1	c.221C>T	p.Thr74Ile	missense_variant	Exon 3 of 3	3		ENSP00000466577.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461380 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726962

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	.;.;T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.70	T;T;T
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.62	D;D;D
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.0	.;.;M
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-5.8	.;.;D
REVEL	Benign	0.23
Sift	Pathogenic	0.0	.;.;D
Sift4G	Pathogenic	0.0	D;.;D
Polyphen		1.0	.;.;D
Vest4		0.50
MutPred		0.32		.;.;Loss of sheet (P = 0.1501);
MVP		0.28
MPC		0.099
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.92
gMVP		0.44

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: chr18-52265120;