chr13-98829756-C-T

Variant names:

• chr13-98829756-C-T
• rs368911408
• NM_001366683.2:c.4636G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001366683.2(DOCK9):​c.4636G>A​(p.Val1546Ile) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000025 in 1,601,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: DOCK9 NM_001366683.2 missense, splice_region
• Scores: Splicing: ADA: 0.9188
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.83
• Publications: 0 publications found

Genes affected

DOCK9 (HGNC:14132): (dedicator of cytokinesis 9) Enables cadherin binding activity. Predicted to be involved in positive regulation of GTPase activity. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

DOCK9-AS1 (HGNC:40672): (DOCK9 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16010705).
• BS2: High AC in GnomAdExome4 at 37 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366683.2. 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
	DOCK9	NM_001366683.2	MANE Select	c.4636G>A	p.Val1546Ile	missense splice_region	Exon 42 of 53	NP_001353612.1	A0A804HIE8
	DOCK9	NM_001366681.2		c.4636G>A	p.Val1546Ile	missense splice_region	Exon 42 of 55	NP_001353610.1
	DOCK9	NM_001366684.2		c.4636G>A	p.Val1546Ile	missense splice_region	Exon 42 of 54	NP_001353613.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK9	ENST00000682017.1	MANE Select	c.4636G>A	p.Val1546Ile	missense splice_region	Exon 42 of 53	ENSP00000507034.1	A0A804HIE8
	DOCK9	ENST00000903387.1		c.4636G>A	p.Val1546Ile	missense splice_region	Exon 43 of 54	ENSP00000573446.1
	DOCK9	ENST00000448493.7	TSL:5	c.4603G>A	p.Val1535Ile	missense splice_region	Exon 42 of 53	ENSP00000401958.4	A0A088AWN3

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152180 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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000176 AC: 4 AN: 227342 AF XY: 0.0000164

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: 0.0000393

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000255 AC: 37 AN: 1448890 Hom.: 0 Cov.: 31 AF XY: 0.0000292 AC XY: 21 AN XY: 719122

African (AFR) AF: 0.00 AC: 0 AN: 33316

American (AMR) AF: 0.00 AC: 0 AN: 43158

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25824

East Asian (EAS) AF: 0.00 AC: 0 AN: 39380

South Asian (SAS) AF: 0.00 AC: 0 AN: 83518

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52722

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.0000335 AC: 37 AN: 1105274

Other (OTH) AF: 0.00 AC: 0 AN: 59946

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152180 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74348

African (AFR) AF: 0.00 AC: 0 AN: 41434

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000113

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000120 AC: 1

ExAC AF: 0.00000828 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	0.10
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	23
DANN	Uncertain	0.99
Eigen	Benign	-0.13
Eigen_PC	Benign	0.038
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.79	T
PhyloP100		3.8
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.054
Sift	Benign	0.33	T
Sift4G	Benign	0.32	T
Polyphen		0.0	B
Vest4		0.15
MVP		0.40
MPC		0.25
ClinPred		0.32	T
GERP RS		4.7
PromoterAI		-0.031	Neutral
gMVP		0.73
Mutation Taster		=61/39	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.92
dbscSNV1_RF	Benign	0.68
SpliceAI score (max)		0.080		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: rs368911408; hg19: chr13-99482010;