Genetic Variant FAM110B:p.Ala214Ser (chr8-58146870-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001377989.1(FAM110B):c.640G>T(p.Ala214Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. A214T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

FAM110B
NM_001377989.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.33

Publications

4 publications found

Variant links:

COSMIC-nc: COSV64065210

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13302588).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM110B	NM_001377989.1 link	c.640G>T	p.Ala214Ser	missense_variant	Exon 4 of 4	ENST00000519262.6	NP_001364918.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FAM110B	ENST00000519262.6 link	c.640G>T	p.Ala214Ser	missense_variant	Exon 4 of 4	2	NM_001377989.1	ENSP00000509301.1	Q8TC76
FAM110B	ENST00000361488.7 link	c.640G>T	p.Ala214Ser	missense_variant	Exon 5 of 5	2		ENSP00000355204.3	Q8TC76
FAM110B	ENST00000520369.5 link	n.427-50961G>T		intron_variant	Intron 3 of 4	4
FAM110B	ENST00000523486.5 link	n.226-42448G>T		intron_variant	Intron 2 of 3	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251212

AF XY:

0.00000737

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461752

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727180

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86238

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111974

Other (OTH)

AF:

0.00

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.025

Eigen

Benign

0.12

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.76

M_CAP

Benign

0.049

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

PhyloP100

4.3

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.26

REVEL

Benign

0.086

Sift

Uncertain

0.018

Sift4G

Benign

0.30

Polyphen

0.48

Vest4

0.062

MutPred

0.18

Gain of relative solvent accessibility (P = 0.0023);

MVP

0.17

MPC

0.64

ClinPred

0.26

GERP RS

5.7

Varity_R

0.090

gMVP

0.19

Mutation Taster

=70/30

polymorphism

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over