Genetic Variant NM_001377989.1:c.1099G>T (chr8-58147329-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001377989.1(FAM110B):c.1099G>T(p.Val367Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,204 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

FAM110B
NM_001377989.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.96

Publications

0 publications found

Variant links:

Genes affected

FAM110B (HGNC:28587): (family with sequence similarity 110 member B) Located in cytosol and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

FAM110B links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377989.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM110B	NM_001377989.1	MANE Select	c.1099G>T	p.Val367Phe	missense	Exon 4 of 4	NP_001364918.1	Q8TC76
FAM110B	NM_001377997.1		c.1099G>T	p.Val367Phe	missense	Exon 3 of 3	NP_001364926.1	Q8TC76
FAM110B	NM_001377998.1		c.1099G>T	p.Val367Phe	missense	Exon 3 of 3	NP_001364927.1	Q8TC76

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM110B	ENST00000519262.6	TSL:2 MANE Select	c.1099G>T	p.Val367Phe	missense	Exon 4 of 4	ENSP00000509301.1	Q8TC76
FAM110B	ENST00000361488.7	TSL:2	c.1099G>T	p.Val367Phe	missense	Exon 5 of 5	ENSP00000355204.3	Q8TC76
FAM110B	ENST00000898541.1		c.1099G>T	p.Val367Phe	missense	Exon 5 of 5	ENSP00000568600.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000399

AC:

AN:

250424

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000616

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461204

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726870

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26028

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86152

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53366

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111648

Other (OTH)

AF:

0.00

AC:

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.75

BayesDel_addAF

Benign

-0.024

BayesDel_noAF

Benign

-0.090

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.031

MetaRNN

Uncertain

0.60

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.6

PhyloP100

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-2.4

REVEL

Uncertain

0.31

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.030

Polyphen

0.99

Vest4

0.78

MutPred

0.16

Loss of relative solvent accessibility (P = 0.0404)

MVP

0.35

MPC

1.8

ClinPred

0.67

GERP RS

5.6

Varity_R

0.48

gMVP

0.76

Mutation Taster

=27/73

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over