NM_020177.3:c.545-1294C>T

Variant names:

• chr5-115526911-G-A
• rs372702
• NM_020177.3:c.545-1294C>T

Variant summary

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

The NM_020177.3(FEM1C):​c.545-1294C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 151,754 control chromosomes in the GnomAD database, including 27,002 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 0.59 (27002 hom., cov: 31)
• Consequence: FEM1C NM_020177.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020177.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FEM1C	NM_020177.3	MANE Select	c.545-1294C>T		intron	N/A	NP_064562.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FEM1C	ENST00000274457.5	TSL:1 MANE Select	c.545-1294C>T		intron	N/A	ENSP00000274457.3

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89492 AN: 151636 Hom.: 26979 Cov.: 31

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.567

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

GnomAD4 genome AF: 0.590 AC: 89553 AN: 151754 Hom.: 27002 Cov.: 31 AF XY: 0.587 AC XY: 43538 AN XY: 74152

African (AFR) AF: 0.704 AC: 29111 AN: 41364

American (AMR) AF: 0.589 AC: 8978 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1693 AN: 3468

East Asian (EAS) AF: 0.689 AC: 3547 AN: 5148

South Asian (SAS) AF: 0.600 AC: 2884 AN: 4804

European-Finnish (FIN) AF: 0.489 AC: 5144 AN: 10530

Middle Eastern (MID) AF: 0.479 AC: 140 AN: 292

European-Non Finnish (NFE) AF: 0.536 AC: 36397 AN: 67886

Other (OTH) AF: 0.571 AC: 1207 AN: 2112

Alfa AF: 0.556 Hom.: 2964

Bravo AF: 0.605

Asia WGS AF: 0.685 AC: 2379 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.22
DANN	Benign	0.36
PhyloP100		-1.4
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: rs372702; hg19: chr5-114862608;