3-75665296-C-A

Variant names:

• chr3-75665296-C-A
• rs75613762
• NM_001124759.5:c.334+93C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001124759.5(FRG2C):​c.334+93C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 53)
  • Exomes 𝑓: 0.0000021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FRG2C NM_001124759.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08
• Publications: 1 publications found

Genes affected

FRG2C (HGNC:33626): (FSHD region gene 2 family member C) Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000293315 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001124759.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRG2C	NM_001124759.5	MANE Select	c.334+93C>A		intron	N/A	NP_001118231.1	A6NGY1
	FRG2C	NM_001410775.1		c.331+93C>A		intron	N/A	NP_001397704.1	C9JUX3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRG2C	ENST00000308062.8	TSL:1 MANE Select	c.334+93C>A		intron	N/A	ENSP00000312299.3	A6NGY1
	FRG2C	ENST00000464571.1	TSL:1	c.331+93C>A		intron	N/A	ENSP00000419432.1	C9JUX3
	ENSG00000293315	ENST00000638439.2	TSL:5	n.185+4724G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 53

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000205 AC: 2 AN: 973668 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 500078

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000436 AC: 1 AN: 22936

American (AMR) AF: 0.00 AC: 0 AN: 34478

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21464

East Asian (EAS) AF: 0.00 AC: 0 AN: 36642

South Asian (SAS) AF: 0.00 AC: 0 AN: 70158

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51062

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4800

European-Non Finnish (NFE) AF: 0.00000145 AC: 1 AN: 688050

Other (OTH) AF: 0.00 AC: 0 AN: 44078

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 53

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.56
DANN	Benign	0.45
PhyloP100		-2.1

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: rs75613762; hg19: chr3-75714447;