rs79777505

Variant names:

• chr10-133626712-G-A
• rs79777505
• NM_001080998.2:c.31C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-133626712-G-A
• chr10-133626712-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001080998.2(FRG2B):​c.31C>T​(p.His11Tyr) variant causes a missense 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H11Q) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FRG2B NM_001080998.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.842
• Publications: 9 publications found

Genes affected

FRG2B (HGNC:33518): (FSHD region gene 2 family member B) Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000288107 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.002344668).
• BP6: Variant 10-133626712-G-A is Benign according to our data. Variant chr10-133626712-G-A is described in ClinVar as Benign. ClinVar VariationId is 402881.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080998.2. 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
	FRG2B	NM_001080998.2	MANE Select	c.31C>T	p.His11Tyr	missense	Exon 1 of 4	NP_001074467.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRG2B	ENST00000425520.2	TSL:1 MANE Select	c.31C>T	p.His11Tyr	missense	Exon 1 of 4	ENSP00000401310.1
	FRG2B	ENST00000443774.5	TSL:1	c.31C>T	p.His11Tyr	missense	Exon 1 of 4	ENSP00000408343.1
	ENSG00000288107	ENST00000655152.1		n.446-821G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.358 AC: 71497 AN: 199604 AF XY: 0.367

Gnomad AFR exome AF: 0.300

Gnomad AMR exome AF: 0.310

Gnomad ASJ exome AF: 0.379

Gnomad EAS exome AF: 0.273

Gnomad FIN exome AF: 0.455

Gnomad NFE exome AF: 0.379

Gnomad OTH exome AF: 0.301

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

Alfa AF: 0.319 Hom.: 0

ExAC AF: 0.491 AC: 59617

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	6.8
DANN	Benign	0.90
DEOGEN2	Benign	0.081	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.53	T
MetaRNN	Benign	0.0023	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.97	L
PhyloP100		0.84
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.046
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.012	D
Polyphen		0.20	B
Vest4		0.27
MPC		1.7
ClinPred		0.019	T
GERP RS		0.11
PromoterAI		-0.015	Neutral
Varity_R		0.18
gMVP		0.015
Mutation Taster		=99/1	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: rs79777505; hg19: chr10-135440216; COSMIC: COSV71042480;