16-57701966-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001289162.2(DRC7):​c.535C>T​(p.Leu179Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DRC7
NM_001289162.2 missense

Scores

3
10
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.49
Variant links:
Genes affected
DRC7 (HGNC:25289): (dynein regulatory complex subunit 7) Predicted to be involved in flagellated sperm motility. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.839

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DRC7NM_001289162.2 linkc.535C>T p.Leu179Phe missense_variant Exon 6 of 19 ENST00000360716.8 NP_001276091.1 Q8IY82-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DRC7ENST00000360716.8 linkc.535C>T p.Leu179Phe missense_variant Exon 6 of 19 1 NM_001289162.2 ENSP00000353942.3 Q8IY82-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251168
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135716
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461850
Hom.:
0
Cov.:
29
AF XY:
0.00000138
AC XY:
1
AN XY:
727226
show subpopulations
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 17, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.535C>T (p.L179F) alteration is located in exon 5 (coding exon 4) of the DRC7 gene. This alteration results from a C to T substitution at nucleotide position 535, causing the leucine (L) at amino acid position 179 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.29
BayesDel_addAF
Pathogenic
0.32
D
BayesDel_noAF
Pathogenic
0.22
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.18
T;.;T
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.49
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.85
.;D;T
M_CAP
Uncertain
0.18
D
MetaRNN
Pathogenic
0.84
D;D;D
MetaSVM
Benign
-0.67
T
PrimateAI
Uncertain
0.60
T
PROVEAN
Uncertain
-3.2
D;D;D
REVEL
Uncertain
0.43
Sift
Uncertain
0.0050
D;D;D
Sift4G
Uncertain
0.0090
D;D;D
Polyphen
1.0
D;.;D
Vest4
0.71
MutPred
0.72
Gain of catalytic residue at L179 (P = 0.003);.;Gain of catalytic residue at L179 (P = 0.003);
MVP
0.73
MPC
0.73
ClinPred
0.97
D
GERP RS
4.1
Varity_R
0.35
gMVP
0.75

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1380649895; hg19: chr16-57735878; API