Genetic Variant DRC5:p.Arg301Leu (chr6-44282504-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_182539.4(DRC5):c.902G>T(p.Arg301Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,322 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. R301Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

DRC5
NM_182539.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.518

Publications

1 publications found

Variant links:

Genes affected

DRC5 (HGNC:11693): (t-complex-associated-testis-expressed 1) Predicted to be involved in flagellated sperm motility. Predicted to be located in sperm flagellum. [provided by Alliance of Genome Resources, Apr 2022]

DRC5 links:

ENSG00000272442 (HGNC:):

ENSG00000272442 links:

TMEM151B (HGNC:21315): (transmembrane protein 151B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM151B links:

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ACMG classification

Classification was made for transcript

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=0.12978977).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182539.4. 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
	DRC5	NM_182539.4	MANE Select	c.902G>T	p.Arg301Leu	missense	Exon 4 of 5	NP_872345.2	Q5JU00

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TCTE1	ENST00000371505.5	TSL:1 MANE Select	c.902G>T	p.Arg301Leu	missense	Exon 4 of 5	ENSP00000360560.4	Q5JU00
ENSG00000272442	ENST00000505802.1	TSL:2	n.312+8998C>A		intron	N/A	ENSP00000424257.1	H0Y9J4
TCTE1	ENST00000897136.1		c.902G>T	p.Arg301Leu	missense	Exon 4 of 5	ENSP00000567195.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1454322

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723714

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46160

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111828

Other (OTH)

AF:

0.00

AC:

AN:

60330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

Cov.:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.078

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.11

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.77

M_CAP

Benign

0.028

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

PhyloP100

0.52

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.14

Sift

Benign

0.14

Sift4G

Benign

0.071

Polyphen

0.42

Vest4

0.22

MVP

0.12

MPC

0.62

ClinPred

0.94

GERP RS

3.6

Varity_R

0.18

gMVP

0.43

Mutation Taster

=83/17

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over