rs12187973

Variant names:

• chr5-115522740-G-T
• rs12187973
• NM_020177.3:c.*1568C>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.*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 NM_020177.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0630
• Publications: 6 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=-0.84).
• 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 rank	MANE	Protein	UniProt
FEM1C	NM_020177.3	c.*1568C>A		3_prime_UTR_variant	Exon 3 of 3	ENST00000274457.5	NP_064562.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FEM1C	ENST00000274457.5	c.*1568C>A		3_prime_UTR_variant	Exon 3 of 3	1	NM_020177.3	ENSP00000274457.3

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.469 AC: 195 AN: 416

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AF: 0.500 AC: 2 AN: 4

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

African (AFR) AF: 0.173 AC: 7187 AN: 41464

American (AMR) AF: 0.469 AC: 7141 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1311 AN: 3460

East Asian (EAS) AF: 0.557 AC: 2870 AN: 5150

South Asian (SAS) AF: 0.496 AC: 2392 AN: 4818

European-Finnish (FIN) AF: 0.423 AC: 4465 AN: 10548

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.444 AC: 30114 AN: 67776

Other (OTH) AF: 0.395 AC: 830 AN: 2102

Alfa AF: 0.418 Hom.: 15562

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
PhyloP100		0.063
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: rs12187973; hg19: chr5-114858437;