5-95392839-A-G

Variant names:

• chr5-95392839-A-G
• rs1582774830
• NM_152548.3:c.170A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152548.3(FAM81B):​c.170A>G​(p.Glu57Gly) 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. 13/19 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)
• Consequence: FAM81B NM_152548.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.99

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

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=0.11643422).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM81B	NM_152548.3	c.170A>G	p.Glu57Gly	missense_variant	Exon 2 of 10	ENST00000283357.10	NP_689761.2
FAM81B	XM_011543207.2	c.170A>G	p.Glu57Gly	missense_variant	Exon 2 of 9		XP_011541509.1
FAM81B	XM_047416821.1	c.170A>G	p.Glu57Gly	missense_variant	Exon 2 of 8		XP_047272777.1
FAM81B	XM_047416822.1	c.170A>G	p.Glu57Gly	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	c.170A>G	p.Glu57Gly	missense_variant	Exon 2 of 10	1	NM_152548.3	ENSP00000283357.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 15, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.170A>G (p.E57G) alteration is located in exon 2 (coding exon 2) of the FAM81B gene. This alteration results from a A to G substitution at nucleotide position 170, causing the glutamic acid (E) at amino acid position 57 to be replaced by a glycine (G). 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	0.081
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	21
DANN	Uncertain	1.0
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.43	N
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.21	N
REVEL	Benign	0.097
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.046	D
Vest4		0.40
MutPred		0.052		Loss of catalytic residue at E57 (P = 0.1257);
MVP		0.29
MPC		0.40
ClinPred		0.64	D
GERP RS		4.5
gMVP		0.051

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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

Other links and lift over

dbSNP: rs1582774830; hg19: chr5-94728543; COSMIC: COSV105107832; COSMIC: COSV105107832;