5-115524700-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_020177.3(FEM1C):c.1462C>T(p.Leu488=) variant causes a synonymous change. The variant allele was found at a frequency of 0.000501 in 1,543,624 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00070 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00048 (5 hom.)
• Consequence: FEM1C NM_020177.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.90

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 5-115524700-G-A is Benign according to our data. Variant chr5-115524700-G-A is described in ClinVar as [Benign]. Clinvar id is 779887.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FEM1C	NM_020177.3	c.1462C>T	p.Leu488=	synonymous_variant	3/3	ENST00000274457.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FEM1C	ENST00000274457.5	c.1462C>T	p.Leu488=	synonymous_variant	3/3	1	NM_020177.3	P1

Frequencies

GnomAD3 genomes AF: 0.000697 AC: 106 AN: 152152 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000590

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0166

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00162 AC: 307 AN: 189108 Hom.: 1 AF XY: 0.00155 AC XY: 154 AN XY: 99474

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0175

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000198

Gnomad OTH exome AF: 0.000685

GnomAD4 exome AF: 0.000479 AC: 666 AN: 1391354 Hom.: 5 Cov.: 31 AF XY: 0.000470 AC XY: 322 AN XY: 685598

Gnomad4 AFR exome AF: 0.0000324

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0150

Gnomad4 SAS exome AF: 0.0000277

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000305

Gnomad4 OTH exome AF: 0.000733

GnomAD4 genome AF: 0.000703 AC: 107 AN: 152270 Hom.: 4 Cov.: 32 AF XY: 0.000766 AC XY: 57 AN XY: 74456

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.000589

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0166

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000108 Hom.: 0

Bravo AF: 0.000654

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 29, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
Cadd	Benign	7.2
Dann	Benign	0.73

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: rs147350117; hg19: chr5-114860397; COSMIC: COSV57232550;