19-17762800-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_015122.3(FCHO1):​c.66C>T​(p.Ser22Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

FCHO1
NM_015122.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.628
Variant links:
Genes affected
FCHO1 (HGNC:29002): (FCH and mu domain containing endocytic adaptor 1) Enables AP-2 adaptor complex binding activity. Involved in clathrin coat assembly and clathrin-dependent endocytosis. Located in cytosol; nucleoplasm; and plasma membrane. Is active in clathrin-coated pit. Implicated in primary immunodeficiency disease. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.32).
BP6
Variant 19-17762800-C-T is Benign according to our data. Variant chr19-17762800-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1574977.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.628 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FCHO1NM_015122.3 linkc.66C>T p.Ser22Ser synonymous_variant Exon 5 of 29 ENST00000596536.6 NP_055937.1 O14526-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FCHO1ENST00000596536.6 linkc.66C>T p.Ser22Ser synonymous_variant Exon 5 of 29 5 NM_015122.3 ENSP00000470731.1 O14526-1
FCHO1ENST00000699212.1 linkc.66C>T p.Ser22Ser synonymous_variant Exon 5 of 30 ENSP00000514208.1 A0A8V8TPN1
FCHO1ENST00000594202.6 linkc.66C>T p.Ser22Ser synonymous_variant Exon 5 of 29 5 ENSP00000473001.1 A0A0C3SFZ9
FCHO1ENST00000596309.6 linkc.66C>T p.Ser22Ser synonymous_variant Exon 5 of 29 4 ENSP00000470511.2 O14526-1M0QZF0
FCHO1ENST00000596951.6 linkc.66C>T p.Ser22Ser synonymous_variant Exon 5 of 29 5 ENSP00000472417.1 O14526-1
FCHO1ENST00000600209.6 linkc.66C>T p.Ser22Ser synonymous_variant Exon 5 of 29 5 ENSP00000469075.2 O14526-1M0QXD1
FCHO1ENST00000600676.5 linkc.66C>T p.Ser22Ser synonymous_variant Exon 4 of 28 2 ENSP00000470493.1 O14526-1
FCHO1ENST00000699176.1 linkc.66C>T p.Ser22Ser synonymous_variant Exon 5 of 29 ENSP00000514179.1 O14526-1
FCHO1ENST00000699177.1 linkc.66C>T p.Ser22Ser synonymous_variant Exon 5 of 29 ENSP00000514180.1 O14526-1
FCHO1ENST00000699207.1 linkc.66C>T p.Ser22Ser synonymous_variant Exon 5 of 29 ENSP00000514204.1 O14526-1
FCHO1ENST00000699209.1 linkc.66C>T p.Ser22Ser synonymous_variant Exon 5 of 29 ENSP00000514206.1 O14526-1
FCHO1ENST00000699215.1 linkc.66C>T p.Ser22Ser synonymous_variant Exon 4 of 28 ENSP00000514211.1 O14526-1
FCHO1ENST00000699202.1 linkc.66C>T p.Ser22Ser synonymous_variant Exon 5 of 29 ENSP00000514200.1 A0A8V8TMX9
FCHO1ENST00000699214.1 linkc.66C>T p.Ser22Ser synonymous_variant Exon 4 of 28 ENSP00000514210.1 A0A8V8TMX9
FCHO1ENST00000699208.1 linkc.66C>T p.Ser22Ser synonymous_variant Exon 5 of 28 ENSP00000514205.1 A0A8V8TPA0
FCHO1ENST00000699198.1 linkc.66C>T p.Ser22Ser synonymous_variant Exon 5 of 29 ENSP00000514196.1 M0QYA9
FCHO1ENST00000699199.1 linkc.66C>T p.Ser22Ser synonymous_variant Exon 4 of 28 ENSP00000514197.1 M0QYA9
FCHO1ENST00000699213.1 linkc.66C>T p.Ser22Ser synonymous_variant Exon 4 of 28 ENSP00000514209.1 M0QYA9
FCHO1ENST00000699197.1 linkc.66C>T p.Ser22Ser synonymous_variant Exon 5 of 28 ENSP00000514195.1 A0A8V8TNC3
FCHO1ENST00000699200.1 linkc.66C>T p.Ser22Ser synonymous_variant Exon 5 of 28 ENSP00000514198.1 A0A8V8TNC3
FCHO1ENST00000699196.1 linkc.66C>T p.Ser22Ser synonymous_variant Exon 5 of 27 ENSP00000514194.1 A0A8V8TP91
FCHO1ENST00000699203 linkc.-85C>T 5_prime_UTR_variant Exon 3 of 22 ENSP00000514201.1 A0A8V8TPM7
FCHO1ENST00000699201.1 linkn.66C>T non_coding_transcript_exon_variant Exon 5 of 28 ENSP00000514199.1 A0A8V8TP96
FCHO1ENST00000699205.1 linkn.66C>T non_coding_transcript_exon_variant Exon 5 of 27 ENSP00000514202.1 A0A8V8TMV7
FCHO1ENST00000699206.1 linkn.66C>T non_coding_transcript_exon_variant Exon 5 of 29 ENSP00000514203.1 A0A8V8TMV7
FCHO1ENST00000699210.1 linkn.66C>T non_coding_transcript_exon_variant Exon 5 of 28 ENSP00000514207.1 A0A8V8TND1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152142
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251454
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135894
show subpopulations
Gnomad AFR exome
AF:
0.0000615
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461770
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727200
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152142
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

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

Submissions by phenotype

not provided Benign:1
Aug 27, 2021
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.32
CADD
Benign
9.8
DANN
Benign
0.88
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: rs778637267; hg19: chr19-17873609; COSMIC: COSV53183330; COSMIC: COSV53183330; API