rs16981943

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-17755179-G-A
• chr19-17755179-G-C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_015122.3(FCHO1):​c.15G>A​(p.Gly5Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G5G) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FCHO1 NM_015122.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.258
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=-0.258 with no splicing effect.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	7.1
DANN	Benign	0.89
PhyloP100		-0.26
PromoterAI		0.038	Neutral

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;