10-45727439-A-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001330074.2(WASHC2C):​c.26A>C​(p.Gln9Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

WASHC2C
NM_001330074.2 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.437

Publications

0 publications found
Variant links:
Genes affected
WASHC2C (HGNC:23414): (WASH complex subunit 2C) Enables phosphatidylinositol phosphate binding activity; phosphatidylinositol-3,4-bisphosphate binding activity; and retromer complex binding activity. Involved in several processes, including endosomal transport; negative regulation of barbed-end actin filament capping; and regulation of substrate adhesion-dependent cell spreading. Located in cytosol; early endosome; and nucleolus. Part of WASH complex. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.059012353).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
WASHC2CNM_001330074.2 linkc.26A>C p.Gln9Pro missense_variant Exon 2 of 31 ENST00000623400.4 NP_001317003.1 Q9Y4E1-7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
WASHC2CENST00000623400.4 linkc.26A>C p.Gln9Pro missense_variant Exon 2 of 31 1 NM_001330074.2 ENSP00000485513.1 Q9Y4E1-7

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1459090
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
725840
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33380
American (AMR)
AF:
0.00
AC:
0
AN:
44656
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26086
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39652
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86124
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53092
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4512
European-Non Finnish (NFE)
AF:
9.00e-7
AC:
1
AN:
1111428
Other (OTH)
AF:
0.00
AC:
0
AN:
60160
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
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
Dec 11, 2023
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.26A>C (p.Q9P) alteration is located in exon 2 (coding exon 2) of the FAM21C gene. This alteration results from a A to C substitution at nucleotide position 26, causing the glutamine (Q) at amino acid position 9 to be replaced by a proline (P). 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
0.065
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
1.8
DANN
Benign
0.54
DEOGEN2
Benign
0.023
T;T;.;.;.;.;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.22
N
LIST_S2
Benign
0.72
T;T;T;T;T;T;T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.059
T;T;T;T;T;T;T
MetaSVM
Benign
-0.97
T
PhyloP100
-0.44
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-1.5
N;N;N;N;N;.;N
REVEL
Benign
0.083
Sift
Benign
0.33
T;T;T;T;T;.;T
Sift4G
Benign
0.29
T;T;T;T;T;T;T
Polyphen
0.0
.;B;.;.;.;.;.
Vest4
0.15
MutPred
0.051
.;Gain of glycosylation at Q9 (P = 0.101);Gain of glycosylation at Q9 (P = 0.101);Gain of glycosylation at Q9 (P = 0.101);Gain of glycosylation at Q9 (P = 0.101);Gain of glycosylation at Q9 (P = 0.101);Gain of glycosylation at Q9 (P = 0.101);
MVP
0.061
ClinPred
0.54
D
GERP RS
0.86
PromoterAI
0.063
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.16
gMVP
0.32
Mutation Taster
=92/8
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs1468205063; hg19: chr10-46222887; API