dbSNP rs756972511: DYNC1I1:p.Arg27Trp (chr7-95804808-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001135556.2(DYNC1I1):c.79C>T(p.Arg27Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000153 in 1,571,654 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

DYNC1I1
NM_001135556.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.527

Publications

1 publications found

Variant links:

Genes affected

DYNC1I1 (HGNC:2963): (dynein cytoplasmic 1 intermediate chain 1) Enables spectrin binding activity. Involved in vesicle transport along microtubule. Located in several cellular components, including kinetochore; recycling endosome; and spindle pole. [provided by Alliance of Genome Resources, Apr 2022]

DYNC1I1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135556.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DYNC1I1	NM_001135556.2	MANE Select	c.79C>T	p.Arg27Trp	missense	Exon 2 of 17	NP_001129028.1	O14576-2
DYNC1I1	NM_004411.5		c.79C>T	p.Arg27Trp	missense	Exon 2 of 17	NP_004402.1	O14576-1
DYNC1I1	NM_001278421.2		c.79C>T	p.Arg27Trp	missense	Exon 2 of 16	NP_001265350.1	O14576-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DYNC1I1	ENST00000447467.6	TSL:1 MANE Select	c.79C>T	p.Arg27Trp	missense	Exon 2 of 17	ENSP00000392337.2	O14576-2
DYNC1I1	ENST00000324972.10	TSL:1	c.79C>T	p.Arg27Trp	missense	Exon 2 of 17	ENSP00000320130.6	O14576-1
DYNC1I1	ENST00000457059.2	TSL:1	c.79C>T	p.Arg27Trp	missense	Exon 2 of 17	ENSP00000412444.1	O14576-2

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151612

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000658

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000106

AC:

AN:

188260

AF XY:

0.0000199

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000340

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000132

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000148

AC:

AN:

1420042

Hom.:

Cov.:

AF XY:

0.0000199

AC XY:

AN XY:

703030

show subpopulations

African (AFR)

AF:

0.0000313

AC:

AN:

31988

American (AMR)

AF:

0.0000247

AC:

AN:

40484

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25418

East Asian (EAS)

AF:

0.00

AC:

AN:

37238

South Asian (SAS)

AF:

0.00

AC:

AN:

81170

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50710

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5706

European-Non Finnish (NFE)

AF:

0.0000156

AC:

AN:

1088586

Other (OTH)

AF:

0.0000340

AC:

AN:

58742

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.415

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151612

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73974

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41202

American (AMR)

AF:

0.0000658

AC:

AN:

15206

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10474

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67966

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000284

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.00000842

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.78

BayesDel_addAF

Uncertain

0.034

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.24

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.87

LIST_S2

Pathogenic

1.0

M_CAP

Uncertain

0.13

MetaRNN

Uncertain

0.44

MetaSVM

Uncertain

0.27

MutationAssessor

Uncertain

2.3

PhyloP100

0.53

PrimateAI

Pathogenic

0.84

PROVEAN

Pathogenic

-4.5

REVEL

Benign

0.25

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.63

MutPred

0.21

Loss of methylation at K28 (P = 0.049)

MVP

0.84

MPC

1.4

ClinPred

0.97

GERP RS

3.7

Varity_R

0.46

gMVP

0.37

Mutation Taster

=44/56

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over