5-95392863-C-G

Variant names:

• chr5-95392863-C-G
• rs750460827
• NM_152548.3:c.194C>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.194C>G​(p.Pro65Arg) 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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P65L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM81B NM_152548.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44
• 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=0.3629699).

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.194C>G	p.Pro65Arg	missense	Exon 2 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.194C>G	p.Pro65Arg	missense	Exon 2 of 10	ENSP00000283357.5	Q96LP2
	FAM81B	ENST00000507832.5	TSL:1	n.41C>G		non_coding_transcript_exon	Exon 1 of 11	ENSP00000423016.1	H0Y947
	FAM81B	ENST00000503099.1	TSL:3	n.11C>G		non_coding_transcript_exon	Exon 1 of 5	ENSP00000423296.1	H0Y979

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000407 AC: 1 AN: 245838 AF XY: 0.00000750

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000895

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Uncertain	1.0
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.84	D
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.4
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.039
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0070	D
Vest4		0.56
MutPred		0.24		Loss of glycosylation at S69 (P = 0.0781)
MVP		0.40
MPC		0.45
ClinPred		0.69	D
GERP RS		3.9
gMVP		0.070
Mutation Taster		=89/11	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: rs750460827; hg19: chr5-94728567;