rs256958

Positions:

• chr5-115542368-A-G

Variant summary

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

The NM_020177.3(FEM1C):​c.544+582T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,140 control chromosomes in the GnomAD database, including 1,471 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 0.13 (1471 hom., cov: 32)
• Consequence: FEM1C NM_020177.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.161

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FEM1C	NM_020177.3	c.544+582T>C		intron_variant		ENST00000274457.5	NP_064562.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FEM1C	ENST00000274457.5	c.544+582T>C		intron_variant		1	NM_020177.3	ENSP00000274457	P1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19865 AN: 152022 Hom.: 1468 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.0989

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.0980

Gnomad FIN AF: 0.0649

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.131 AC: 19872 AN: 152140 Hom.: 1471 Cov.: 32 AF XY: 0.126 AC XY: 9383 AN XY: 74398

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.0987

Gnomad4 FIN AF: 0.0649

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.133

Alfa AF: 0.129 Hom.: 799

Bravo AF: 0.137

Asia WGS AF: 0.101 AC: 351 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.9
DANN	Benign	0.70

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: rs256958; hg19: chr5-114878065;