3-75665679-C-T

Variant names:

• chr3-75665679-C-T
• rs1228157109
• NM_001124759.5:c.487C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001124759.5(FRG2C):​c.487C>T​(p.Arg163Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,611,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R163R) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 63)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: FRG2C NM_001124759.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.943
• 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.22353959).

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.487C>T	p.Arg163Trp	missense	Exon 4 of 4	NP_001118231.1	A6NGY1
	FRG2C	NM_001410775.1		c.484C>T	p.Arg162Trp	missense	Exon 4 of 4	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.487C>T	p.Arg163Trp	missense	Exon 4 of 4	ENSP00000312299.3	A6NGY1
	FRG2C	ENST00000464571.1	TSL:1	c.484C>T	p.Arg162Trp	missense	Exon 4 of 4	ENSP00000419432.1	C9JUX3
	ENSG00000293315	ENST00000638439.2	TSL:5	n.185+4341G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000668 AC: 1 AN: 149762 Hom.: 0 Cov.: 63

Gnomad AFR AF: 0.0000246

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000164 AC: 24 AN: 1461642 Hom.: 0 Cov.: 183 AF XY: 0.0000165 AC XY: 12 AN XY: 727136

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

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.000224 AC: 10 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86246

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5762

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111828

Other (OTH) AF: 0.0000166 AC: 1 AN: 60378

⚠️ 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 AF: 0.00000668 AC: 1 AN: 149762 Hom.: 0 Cov.: 63 AF XY: 0.00 AC XY: 0 AN XY: 73022

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

African (AFR) AF: 0.0000246 AC: 1 AN: 40688

American (AMR) AF: 0.00 AC: 0 AN: 14998

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3432

East Asian (EAS) AF: 0.00 AC: 0 AN: 5014

South Asian (SAS) AF: 0.00 AC: 0 AN: 4688

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67288

Other (OTH) AF: 0.00 AC: 0 AN: 2044

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.072	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0012	N
LIST_S2	Benign	0.72	T
M_CAP	Pathogenic	0.73	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		-0.94
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.11
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.95	P
Vest4		0.14
MutPred		0.38		Gain of glycosylation at S162 (P = 0.0134)
MVP		0.38
ClinPred		0.91	D
GERP RS		-1.4
Varity_R		0.15
gMVP		0.0097
Mutation Taster		=99/1	polymorphism

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: rs1228157109; hg19: chr3-75714830;