NM_015122.3:c.15G>C

Variant names:

• chr19-17755179-G-C
• rs16981943
• NM_015122.3:c.15G>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_015122.3(FCHO1):​c.15G>C​(p.Gly5Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00276 in 1,610,978 control chromosomes in the GnomAD database, including 105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (64 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (41 hom.)
• Consequence: FCHO1 NM_015122.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.258
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• immunodeficiency 76

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 19-17755179-G-C is Benign according to our data. Variant chr19-17755179-G-C is described in ClinVar as [Benign]. Clinvar id is 1164702.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.258 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCHO1	NM_015122.3	c.15G>C	p.Gly5Gly	synonymous_variant	Exon 4 of 29	ENST00000596536.6	NP_055937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCHO1	ENST00000596536.6	c.15G>C	p.Gly5Gly	synonymous_variant	Exon 4 of 29	5	NM_015122.3	ENSP00000470731.1
FCHO1	ENST00000699212.1	c.15G>C	p.Gly5Gly	synonymous_variant	Exon 4 of 30			ENSP00000514208.1
FCHO1	ENST00000594202.6	c.15G>C	p.Gly5Gly	synonymous_variant	Exon 4 of 29	5		ENSP00000473001.1
FCHO1	ENST00000596309.6	c.15G>C	p.Gly5Gly	synonymous_variant	Exon 4 of 29	4		ENSP00000470511.2
FCHO1	ENST00000596951.6	c.15G>C	p.Gly5Gly	synonymous_variant	Exon 4 of 29	5		ENSP00000472417.1
FCHO1	ENST00000600209.6	c.15G>C	p.Gly5Gly	synonymous_variant	Exon 4 of 29	5		ENSP00000469075.2
FCHO1	ENST00000600676.5	c.15G>C	p.Gly5Gly	synonymous_variant	Exon 3 of 28	2		ENSP00000470493.1
FCHO1	ENST00000699176.1	c.15G>C	p.Gly5Gly	synonymous_variant	Exon 4 of 29			ENSP00000514179.1
FCHO1	ENST00000699177.1	c.15G>C	p.Gly5Gly	synonymous_variant	Exon 4 of 29			ENSP00000514180.1
FCHO1	ENST00000699207.1	c.15G>C	p.Gly5Gly	synonymous_variant	Exon 4 of 29			ENSP00000514204.1
FCHO1	ENST00000699209.1	c.15G>C	p.Gly5Gly	synonymous_variant	Exon 4 of 29			ENSP00000514206.1
FCHO1	ENST00000699215.1	c.15G>C	p.Gly5Gly	synonymous_variant	Exon 3 of 28			ENSP00000514211.1
FCHO1	ENST00000699202.1	c.15G>C	p.Gly5Gly	synonymous_variant	Exon 4 of 29			ENSP00000514200.1
FCHO1	ENST00000699214.1	c.15G>C	p.Gly5Gly	synonymous_variant	Exon 3 of 28			ENSP00000514210.1
FCHO1	ENST00000699208.1	c.15G>C	p.Gly5Gly	synonymous_variant	Exon 4 of 28			ENSP00000514205.1
FCHO1	ENST00000699198.1	c.15G>C	p.Gly5Gly	synonymous_variant	Exon 4 of 29			ENSP00000514196.1
FCHO1	ENST00000699199.1	c.15G>C	p.Gly5Gly	synonymous_variant	Exon 3 of 28			ENSP00000514197.1
FCHO1	ENST00000699213.1	c.15G>C	p.Gly5Gly	synonymous_variant	Exon 3 of 28			ENSP00000514209.1
FCHO1	ENST00000699197.1	c.15G>C	p.Gly5Gly	synonymous_variant	Exon 4 of 28			ENSP00000514195.1
FCHO1	ENST00000699200.1	c.15G>C	p.Gly5Gly	synonymous_variant	Exon 4 of 28			ENSP00000514198.1
FCHO1	ENST00000699196.1	c.15G>C	p.Gly5Gly	synonymous_variant	Exon 4 of 27			ENSP00000514194.1
FCHO1	ENST00000699201.1	n.15G>C		non_coding_transcript_exon_variant	Exon 4 of 28			ENSP00000514199.1
FCHO1	ENST00000699205.1	n.15G>C		non_coding_transcript_exon_variant	Exon 4 of 27			ENSP00000514202.1
FCHO1	ENST00000699206.1	n.15G>C		non_coding_transcript_exon_variant	Exon 4 of 29			ENSP00000514203.1
FCHO1	ENST00000699210.1	n.15G>C		non_coding_transcript_exon_variant	Exon 4 of 28			ENSP00000514207.1
FCHO1	ENST00000699203.1	c.-124+713G>C		intron_variant	Intron 2 of 21			ENSP00000514201.1

Frequencies

GnomAD3 genomes AF: 0.0153 AC: 2326 AN: 152084 Hom.: 63 Cov.: 32

Gnomad AFR AF: 0.0535

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00590

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00716

GnomAD2 exomes AF: 0.00411 AC: 1017 AN: 247672 AF XY: 0.00310

Gnomad AFR exome AF: 0.0550

Gnomad AMR exome AF: 0.00321

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000803

Gnomad OTH exome AF: 0.00183

GnomAD4 exome AF: 0.00146 AC: 2127 AN: 1458776 Hom.: 41 Cov.: 30 AF XY: 0.00125 AC XY: 904 AN XY: 725720

African (AFR) AF: 0.0528 AC: 1758 AN: 33264

American (AMR) AF: 0.00344 AC: 151 AN: 43924

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25946

East Asian (EAS) AF: 0.00 AC: 0 AN: 39578

South Asian (SAS) AF: 0.0000814 AC: 7 AN: 86004

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53356

Middle Eastern (MID) AF: 0.000696 AC: 4 AN: 5750

European-Non Finnish (NFE) AF: 0.0000270 AC: 30 AN: 1110696

Other (OTH) AF: 0.00294 AC: 177 AN: 60258

GnomAD4 genome AF: 0.0153 AC: 2327 AN: 152202 Hom.: 64 Cov.: 32 AF XY: 0.0149 AC XY: 1110 AN XY: 74430

African (AFR) AF: 0.0533 AC: 2215 AN: 41520

American (AMR) AF: 0.00589 AC: 90 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 67998

Other (OTH) AF: 0.00709 AC: 15 AN: 2116

Alfa AF: 0.00436 Hom.: 3

Bravo AF: 0.0167

Asia WGS AF: 0.00462 AC: 16 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	6.6
DANN	Benign	0.75
PhyloP100		-0.26
PromoterAI		0.077	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16981943; hg19: chr19-17865988;