Genetic Variant FCHO1:p.Ser22Ser (chr19-17762800-C-T) – ACMG Classification: Likely_benign (-3 pts)

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

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]

FCHO1 links:

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
FCHO1	NM_015122.3 link	c.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	UniProt
FCHO1	ENST00000596536.6 link	c.66C>T	p.Ser22Ser	synonymous_variant	Exon 5 of 29	5	NM_015122.3	ENSP00000470731.1	O14526-1
FCHO1	ENST00000699212.1 link	c.66C>T	p.Ser22Ser	synonymous_variant	Exon 5 of 30			ENSP00000514208.1	A0A8V8TPN1
FCHO1	ENST00000594202.6 link	c.66C>T	p.Ser22Ser	synonymous_variant	Exon 5 of 29	5		ENSP00000473001.1	A0A0C3SFZ9
FCHO1	ENST00000596309.6 link	c.66C>T	p.Ser22Ser	synonymous_variant	Exon 5 of 29	4		ENSP00000470511.2	O14526-1M0QZF0
FCHO1	ENST00000596951.6 link	c.66C>T	p.Ser22Ser	synonymous_variant	Exon 5 of 29	5		ENSP00000472417.1	O14526-1
FCHO1	ENST00000600209.6 link	c.66C>T	p.Ser22Ser	synonymous_variant	Exon 5 of 29	5		ENSP00000469075.2	O14526-1M0QXD1
FCHO1	ENST00000600676.5 link	c.66C>T	p.Ser22Ser	synonymous_variant	Exon 4 of 28	2		ENSP00000470493.1	O14526-1
FCHO1	ENST00000699176.1 link	c.66C>T	p.Ser22Ser	synonymous_variant	Exon 5 of 29			ENSP00000514179.1	O14526-1
FCHO1	ENST00000699177.1 link	c.66C>T	p.Ser22Ser	synonymous_variant	Exon 5 of 29			ENSP00000514180.1	O14526-1
FCHO1	ENST00000699207.1 link	c.66C>T	p.Ser22Ser	synonymous_variant	Exon 5 of 29			ENSP00000514204.1	O14526-1
FCHO1	ENST00000699209.1 link	c.66C>T	p.Ser22Ser	synonymous_variant	Exon 5 of 29			ENSP00000514206.1	O14526-1
FCHO1	ENST00000699215.1 link	c.66C>T	p.Ser22Ser	synonymous_variant	Exon 4 of 28			ENSP00000514211.1	O14526-1
FCHO1	ENST00000699202.1 link	c.66C>T	p.Ser22Ser	synonymous_variant	Exon 5 of 29			ENSP00000514200.1	A0A8V8TMX9
FCHO1	ENST00000699214.1 link	c.66C>T	p.Ser22Ser	synonymous_variant	Exon 4 of 28			ENSP00000514210.1	A0A8V8TMX9
FCHO1	ENST00000699208.1 link	c.66C>T	p.Ser22Ser	synonymous_variant	Exon 5 of 28			ENSP00000514205.1	A0A8V8TPA0
FCHO1	ENST00000699198.1 link	c.66C>T	p.Ser22Ser	synonymous_variant	Exon 5 of 29			ENSP00000514196.1	M0QYA9
FCHO1	ENST00000699199.1 link	c.66C>T	p.Ser22Ser	synonymous_variant	Exon 4 of 28			ENSP00000514197.1	M0QYA9
FCHO1	ENST00000699213.1 link	c.66C>T	p.Ser22Ser	synonymous_variant	Exon 4 of 28			ENSP00000514209.1	M0QYA9
FCHO1	ENST00000699197.1 link	c.66C>T	p.Ser22Ser	synonymous_variant	Exon 5 of 28			ENSP00000514195.1	A0A8V8TNC3
FCHO1	ENST00000699200.1 link	c.66C>T	p.Ser22Ser	synonymous_variant	Exon 5 of 28			ENSP00000514198.1	A0A8V8TNC3
FCHO1	ENST00000699196.1 link	c.66C>T	p.Ser22Ser	synonymous_variant	Exon 5 of 27			ENSP00000514194.1	A0A8V8TP91
FCHO1	ENST00000699203 link	c.-85C>T		5_prime_UTR_variant	Exon 3 of 22			ENSP00000514201.1	A0A8V8TPM7
FCHO1	ENST00000699201.1 link	n.66C>T		non_coding_transcript_exon_variant	Exon 5 of 28			ENSP00000514199.1	A0A8V8TP96
FCHO1	ENST00000699205.1 link	n.66C>T		non_coding_transcript_exon_variant	Exon 5 of 27			ENSP00000514202.1	A0A8V8TMV7
FCHO1	ENST00000699206.1 link	n.66C>T		non_coding_transcript_exon_variant	Exon 5 of 29			ENSP00000514203.1	A0A8V8TMV7
FCHO1	ENST00000699210.1 link	n.66C>T		non_coding_transcript_exon_variant	Exon 5 of 28			ENSP00000514207.1	A0A8V8TND1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152142

Hom.:

Cov.:

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:

AN:

251454

Hom.:

AF XY:

0.00000736

AC XY:

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:

AN:

1461770

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

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:

AN:

152142

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over