5-95420363-A-G

Variant names:

• chr5-95420363-A-G
• rs777304233
• NM_152548.3:c.617A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152548.3(FAM81B):​c.617A>G​(p.His206Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,552 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: FAM81B NM_152548.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.77
• Publications: 0 publications found

Genes affected

FAM81B (HGNC:26335): (family with sequence similarity 81 member B) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3899012).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152548.3. 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
	FAM81B	NM_152548.3	MANE Select	c.617A>G	p.His206Arg	missense	Exon 5 of 10	NP_689761.2	Q96LP2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM81B	ENST00000283357.10	TSL:1 MANE Select	c.617A>G	p.His206Arg	missense	Exon 5 of 10	ENSP00000283357.5	Q96LP2
	FAM81B	ENST00000507832.5	TSL:1	n.464A>G		non_coding_transcript_exon	Exon 4 of 11	ENSP00000423016.1	H0Y947
	FAM81B	ENST00000503099.1	TSL:3	n.*274A>G		non_coding_transcript_exon	Exon 4 of 5	ENSP00000423296.1	H0Y979

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000802 AC: 2 AN: 249438 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000111

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461552 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727078

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111760

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	Pathogenic	0.59
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	23
DANN	Uncertain	0.99
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-1.1	T
PhyloP100		3.8
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.091
Sift	Benign	0.038	D
Sift4G	Uncertain	0.052	T
Vest4		0.54
MutPred		0.45		Gain of MoRF binding (P = 0.0211)
MVP		0.27
MPC		0.26
ClinPred		0.67	D
GERP RS		4.7
gMVP		0.52
Mutation Taster		=76/24	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: rs777304233; hg19: chr5-94756067;