chr8-125024791-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_014846.4(WASHC5):​c.3424-118T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0729 in 721,150 control chromosomes in the GnomAD database, including 2,396 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.063 ( 437 hom., cov: 31)
Exomes 𝑓: 0.075 ( 1959 hom. )

Consequence

WASHC5
NM_014846.4 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.421
Variant links:
Genes affected
WASHC5 (HGNC:28984): (WASH complex subunit 5) This gene encodes a 134 kDa protein named strumpellin that is predicted to have multiple transmembrane domains and a spectrin-repeat-containing domain. This ubiquitously expressed gene has its highest expression in skeletal muscle. The protein is named for Strumpell disease; a form of hereditary spastic paraplegia (HSP). Spastic paraplegias are a diverse group of disorders in which the autosomal dominant forms are characterized by progressive, lower extremity spasticity caused by axonal degeneration in the terminal portions of the longest descending and ascending corticospinal tracts. More than 30 loci (SPG1-33) have been implicated in hereditary spastic paraplegia diseases. [provided by RefSeq, Aug 2009]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 8-125024791-A-G is Benign according to our data. Variant chr8-125024791-A-G is described in ClinVar as [Benign]. Clinvar id is 1278382.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0879 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
WASHC5NM_014846.4 linkuse as main transcriptc.3424-118T>C intron_variant ENST00000318410.12 NP_055661.3
WASHC5NM_001330609.2 linkuse as main transcriptc.2980-118T>C intron_variant NP_001317538.1
WASHC5XM_047422502.1 linkuse as main transcriptc.3424-118T>C intron_variant XP_047278458.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
WASHC5ENST00000318410.12 linkuse as main transcriptc.3424-118T>C intron_variant 1 NM_014846.4 ENSP00000318016 P1
WASHC5ENST00000517845.5 linkuse as main transcriptc.2980-118T>C intron_variant 2 ENSP00000429676
WASHC5ENST00000519042.2 linkuse as main transcriptn.563-118T>C intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.0632
AC:
9601
AN:
151876
Hom.:
437
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0153
Gnomad AMI
AF:
0.0824
Gnomad AMR
AF:
0.0756
Gnomad ASJ
AF:
0.150
Gnomad EAS
AF:
0.000194
Gnomad SAS
AF:
0.0238
Gnomad FIN
AF:
0.0793
Gnomad MID
AF:
0.0696
Gnomad NFE
AF:
0.0897
Gnomad OTH
AF:
0.0718
GnomAD4 exome
AF:
0.0754
AC:
42938
AN:
569156
Hom.:
1959
AF XY:
0.0737
AC XY:
22490
AN XY:
305356
show subpopulations
Gnomad4 AFR exome
AF:
0.0151
Gnomad4 AMR exome
AF:
0.0531
Gnomad4 ASJ exome
AF:
0.145
Gnomad4 EAS exome
AF:
0.0000627
Gnomad4 SAS exome
AF:
0.0240
Gnomad4 FIN exome
AF:
0.0811
Gnomad4 NFE exome
AF:
0.0915
Gnomad4 OTH exome
AF:
0.0771
GnomAD4 genome
AF:
0.0632
AC:
9599
AN:
151994
Hom.:
437
Cov.:
31
AF XY:
0.0611
AC XY:
4539
AN XY:
74284
show subpopulations
Gnomad4 AFR
AF:
0.0152
Gnomad4 AMR
AF:
0.0755
Gnomad4 ASJ
AF:
0.150
Gnomad4 EAS
AF:
0.000194
Gnomad4 SAS
AF:
0.0238
Gnomad4 FIN
AF:
0.0793
Gnomad4 NFE
AF:
0.0897
Gnomad4 OTH
AF:
0.0706
Alfa
AF:
0.0691
Hom.:
72
Bravo
AF:
0.0614
Asia WGS
AF:
0.0100
AC:
36
AN:
3478

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJun 26, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
5.7
DANN
Benign
0.73

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

LitVar

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

Other links and lift over

dbSNP: rs17398450; hg19: chr8-126037033; API