NM_152548.3:c.13T>C

Variant names:

• chr5-95391402-T-C
• rs746999587
• NM_152548.3:c.13T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_152548.3(FAM81B):​c.13T>C​(p.Phe5Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000685 in 1,460,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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: 0.0000068 (0 hom.)
• Consequence: FAM81B NM_152548.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.232
• Publications: 1 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]

ENSG00000310288 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.055674165).

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.13T>C	p.Phe5Leu	missense	Exon 1 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.13T>C	p.Phe5Leu	missense	Exon 1 of 10	ENSP00000283357.5	Q96LP2
	ENSG00000310288	ENST00000848849.1		n.-165A>G		upstream_gene	N/A
	ENSG00000310288	ENST00000848850.1		n.-172A>G		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 249184 AF XY: 0.00000740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000167

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000685 AC: 10 AN: 1460818 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 726706

African (AFR) AF: 0.00 AC: 0 AN: 33396

American (AMR) AF: 0.00 AC: 0 AN: 44568

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.000202 AC: 8 AN: 39660

South Asian (SAS) AF: 0.00 AC: 0 AN: 86156

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111462

Other (OTH) AF: 0.0000331 AC: 2 AN: 60348

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000166 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	0.62
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	15
DANN	Uncertain	0.99
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.058	N
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.23
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.041
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.15
MutPred		0.17		Loss of MoRF binding (P = 0.1405)
MVP		0.21
MPC		0.10
ClinPred		0.12	T
GERP RS		1.8
PromoterAI		0.0032	Neutral
gMVP		0.039
Mutation Taster		=98/2	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: rs746999587; hg19: chr5-94727106;