Genetic Variant FAM81B:p.Gly68Asp (chr5-95392872-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152548.3(FAM81B):c.203G>A(p.Gly68Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,458,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

FAM81B
NM_152548.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.705

Variant links:

Genes affected

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

FAM81B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14384219).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM81B	NM_152548.3 link	c.203G>A	p.Gly68Asp	missense_variant	Exon 2 of 10	ENST00000283357.10	NP_689761.2	Q96LP2
FAM81B	XM_011543207.2 link	c.203G>A	p.Gly68Asp	missense_variant	Exon 2 of 9		XP_011541509.1
FAM81B	XM_047416821.1 link	c.203G>A	p.Gly68Asp	missense_variant	Exon 2 of 8		XP_047272777.1
FAM81B	XM_047416822.1 link	c.203G>A	p.Gly68Asp	missense_variant	Exon 2 of 6		XP_047272778.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM81B	ENST00000283357.10 link	c.203G>A	p.Gly68Asp	missense_variant	Exon 2 of 10	1	NM_152548.3	ENSP00000283357.5		Q96LP2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000817

AC:

AN:

244666

Hom.:

AF XY:

0.00

AC XY:

AN XY:

132748

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000113

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1458536

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725356

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 27, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.203G>A (p.G68D) alteration is located in exon 2 (coding exon 2) of the FAM81B gene. This alteration results from a G to A substitution at nucleotide position 203, causing the glycine (G) at amino acid position 68 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.034

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.034

FATHMM_MKL

Benign

0.66

M_CAP

Benign

0.0040

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.48

REVEL

Benign

0.055

Sift

Pathogenic

0.0

Sift4G

Benign

0.21

Vest4

0.35

MutPred

0.20

Gain of relative solvent accessibility (P = 0.0479);

MVP

0.38

MPC

0.16

ClinPred

0.38

GERP RS

2.6

gMVP

0.031

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over