5-115532223-A-T

Variant names:

• chr5-115532223-A-T
• rs17472710
• NM_020177.3:c.545-6606T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020177.3(FEM1C):​c.545-6606T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0541 in 152,164 control chromosomes in the GnomAD database, including 250 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.054 (250 hom., cov: 32)
• Consequence: FEM1C NM_020177.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.359
• Publications: 1 publications found

Genes affected

FEM1C (HGNC:16933): (fem-1 homolog C) Enables ubiquitin ligase-substrate adaptor activity. Involved in ubiquitin-dependent protein catabolic process via the C-end degron rule pathway. Located in cytosol and nucleoplasm. Part of Cul2-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

FEM1C Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Illumina

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FEM1C	NM_020177.3	c.545-6606T>A		intron_variant	Intron 2 of 2	ENST00000274457.5	NP_064562.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FEM1C	ENST00000274457.5	c.545-6606T>A		intron_variant	Intron 2 of 2	1	NM_020177.3	ENSP00000274457.3

Frequencies

GnomAD3 genomes AF: 0.0541 AC: 8230 AN: 152046 Hom.: 250 Cov.: 32

Gnomad AFR AF: 0.0554

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0557

Gnomad ASJ AF: 0.0905

Gnomad EAS AF: 0.0272

Gnomad SAS AF: 0.0724

Gnomad FIN AF: 0.0414

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0540

Gnomad OTH AF: 0.0589

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0541 AC: 8232 AN: 152164 Hom.: 250 Cov.: 32 AF XY: 0.0539 AC XY: 4010 AN XY: 74392

African (AFR) AF: 0.0553 AC: 2296 AN: 41530

American (AMR) AF: 0.0555 AC: 848 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0905 AC: 314 AN: 3468

East Asian (EAS) AF: 0.0273 AC: 141 AN: 5172

South Asian (SAS) AF: 0.0735 AC: 355 AN: 4828

European-Finnish (FIN) AF: 0.0414 AC: 439 AN: 10608

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0540 AC: 3667 AN: 67966

Other (OTH) AF: 0.0582 AC: 123 AN: 2112

Alfa AF: 0.0115 Hom.: 3

Bravo AF: 0.0539

Asia WGS AF: 0.0520 AC: 181 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.4
DANN	Benign	0.70
PhyloP100		0.36
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: rs17472710; hg19: chr5-114867920;