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GeneBe

5-141644350-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_033449.3(FCHSD1):c.1731C>T(p.Pro577=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00553 in 1,613,960 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0041 ( 3 hom., cov: 33)
Exomes 𝑓: 0.0057 ( 38 hom. )

Consequence

FCHSD1
NM_033449.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.15
Variant links:
Genes affected
FCHSD1 (HGNC:25463): (FCH and double SH3 domains 1) Predicted to enable lipid binding activity. Predicted to be involved in neuromuscular synaptic transmission and positive regulation of actin filament polymerization. Predicted to be located in cell projection and perikaryon. Predicted to be active in neuromuscular junction and recycling endosome. Predicted to colocalize with cuticular plate. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-141644350-G-A is Benign according to our data. Variant chr5-141644350-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2655870.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=3.14 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 3 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FCHSD1NM_033449.3 linkuse as main transcriptc.1731C>T p.Pro577= synonymous_variant 17/20 ENST00000435817.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FCHSD1ENST00000435817.7 linkuse as main transcriptc.1731C>T p.Pro577= synonymous_variant 17/201 NM_033449.3 P1Q86WN1-1
FCHSD1ENST00000522783.5 linkuse as main transcriptc.1509C>T p.Pro503= synonymous_variant 16/205
FCHSD1ENST00000523856.5 linkuse as main transcriptn.1400C>T non_coding_transcript_exon_variant 8/112
FCHSD1ENST00000522126.5 linkuse as main transcriptc.*269C>T 3_prime_UTR_variant, NMD_transcript_variant 16/192 Q86WN1-3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00407
AC:
620
AN:
152180
Hom.:
3
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00101
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00190
Gnomad ASJ
AF:
0.0213
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00103
Gnomad FIN
AF:
0.00207
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.00637
Gnomad OTH
AF:
0.00575
GnomAD3 exomes
AF:
0.00483
AC:
1203
AN:
248966
Hom.:
2
AF XY:
0.00447
AC XY:
604
AN XY:
135092
show subpopulations
Gnomad AFR exome
AF:
0.000905
Gnomad AMR exome
AF:
0.00223
Gnomad ASJ exome
AF:
0.0207
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000817
Gnomad FIN exome
AF:
0.00279
Gnomad NFE exome
AF:
0.00699
Gnomad OTH exome
AF:
0.00496
GnomAD4 exome
AF:
0.00568
AC:
8302
AN:
1461662
Hom.:
38
Cov.:
33
AF XY:
0.00555
AC XY:
4036
AN XY:
727110
show subpopulations
Gnomad4 AFR exome
AF:
0.000866
Gnomad4 AMR exome
AF:
0.00228
Gnomad4 ASJ exome
AF:
0.0199
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00106
Gnomad4 FIN exome
AF:
0.00363
Gnomad4 NFE exome
AF:
0.00618
Gnomad4 OTH exome
AF:
0.00704
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00407
AC:
620
AN:
152298
Hom.:
3
Cov.:
33
AF XY:
0.00388
AC XY:
289
AN XY:
74476
show subpopulations
Gnomad4 AFR
AF:
0.00101
Gnomad4 AMR
AF:
0.00190
Gnomad4 ASJ
AF:
0.0213
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00104
Gnomad4 FIN
AF:
0.00207
Gnomad4 NFE
AF:
0.00637
Gnomad4 OTH
AF:
0.00569
Alfa
AF:
0.00691
Hom.:
6
Bravo
AF:
0.00382
Asia WGS
AF:
0.00115
AC:
5
AN:
3478
EpiCase
AF:
0.00567
EpiControl
AF:
0.00593

ClinVar

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

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenMar 01, 2023FCHSD1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.54
Cadd
Benign
6.7
Dann
Benign
0.81
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs150119878; hg19: chr5-141023917; COSMIC: COSV51837279; COSMIC: COSV51837279; API