dbSNP rs765866502: DRC9:p.Lys395Arg (chr3-197891459-T-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_032263.5(DRC9):c.1184A>G(p.Lys395Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000695 in 1,583,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000063 ( 0 hom. )

Consequence

DRC9
NM_032263.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.459

Publications

0 publications found

Variant links:

Genes affected

DRC9 (HGNC:25251): (IQ motif containing G) Enables Hsp70 protein binding activity and calmodulin binding activity. Predicted to be involved in sperm axoneme assembly. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

DRC9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.038035065).

BP6

Variant 3-197891459-T-C is Benign according to our data. Variant chr3-197891459-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3286362.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032263.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DRC9	NM_032263.5	MANE Select	c.1184A>G	p.Lys395Arg	missense	Exon 11 of 12	NP_115639.1	Q9H095-1
DRC9	NM_001134435.3		c.1184A>G	p.Lys395Arg	missense	Exon 10 of 11	NP_001127907.1	Q9H095-1
DRC9	NM_001323027.2		c.1184A>G	p.Lys395Arg	missense	Exon 10 of 11	NP_001309956.1	Q9H095-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IQCG	ENST00000265239.11	TSL:1 MANE Select	c.1184A>G	p.Lys395Arg	missense	Exon 11 of 12	ENSP00000265239.6	Q9H095-1
IQCG	ENST00000960928.1		c.1316A>G	p.Lys439Arg	missense	Exon 12 of 13	ENSP00000630987.1
IQCG	ENST00000960931.1		c.1316A>G	p.Lys439Arg	missense	Exon 11 of 12	ENSP00000630990.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000438

AC:

AN:

251296

AF XY:

0.0000589

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000598

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000629

AC:

AN:

1431550

Hom.:

Cov.:

AF XY:

0.00000700

AC XY:

AN XY:

714292

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32862

American (AMR)

AF:

0.00

AC:

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25980

East Asian (EAS)

AF:

0.000228

AC:

AN:

39536

South Asian (SAS)

AF:

0.00

AC:

AN:

85632

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5728

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1084412

Other (OTH)

AF:

0.00

AC:

AN:

59328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

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:

0.0000131

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41468

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000384

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68042

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

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:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000247

AC:

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.73

CADD

Benign

5.2

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.034

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.59

M_CAP

Benign

0.0053

MetaRNN

Benign

0.038

MetaSVM

Benign

-0.99

PhyloP100

-0.46

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.85

REVEL

Benign

0.028

Sift

Benign

0.46

Sift4G

Benign

0.47

Polyphen

0.034

Vest4

0.14

MutPred

0.41

Loss of ubiquitination at K395 (P = 0.0446)

MVP

0.29

MPC

0.20

ClinPred

0.017

GERP RS

-4.7

Varity_R

0.12

gMVP

0.18

Mutation Taster

=88/12

polymorphism

(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