rs12187973

Positions:

• chr5-115522740-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000274457.5(FEM1C):​c.*1568C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 152,164 control chromosomes in the GnomAD database, including 12,033 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 0.37 (11987 hom., cov: 32)
  • Exomes 𝑓: 0.47 (46 hom.)
• Consequence: FEM1C ENST00000274457.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0630

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FEM1C	NM_020177.3	c.*1568C>A		3_prime_UTR_variant	3/3	ENST00000274457.5	NP_064562.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FEM1C	ENST00000274457.5	c.*1568C>A		3_prime_UTR_variant	3/3	1	NM_020177.3	ENSP00000274457	P1

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56785 AN: 151624 Hom.: 11979 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.390

GnomAD4 exome AF: 0.472 AC: 199 AN: 422 Hom.: 46 Cov.: 0 AF XY: 0.473 AC XY: 121 AN XY: 256

Gnomad4 FIN exome AF: 0.469

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.374 AC: 56793 AN: 151742 Hom.: 11987 Cov.: 32 AF XY: 0.377 AC XY: 27951 AN XY: 74166

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.469

Gnomad4 ASJ AF: 0.379

Gnomad4 EAS AF: 0.557

Gnomad4 SAS AF: 0.496

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.444

Gnomad4 OTH AF: 0.395

Alfa AF: 0.425 Hom.: 12683

Bravo AF: 0.371

Asia WGS AF: 0.548 AC: 1899 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.0
DANN	Benign	0.72

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

Other links and lift over

dbSNP: rs12187973; hg19: chr5-114858437;