Variant 10-14530377-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_031453.4(FAM107B):c.608G>A(p.Arg203Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,461,704 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R203W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

FAM107B
NM_031453.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.83

Variant links:

Genes affected

FAM107B (HGNC:23726): (family with sequence similarity 107 member B) Predicted to act upstream of or within sensory perception of sound. [provided by Alliance of Genome Resources, Apr 2022]

FAM107B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM107B	NM_031453.4 linkuse as main transcript	c.608G>A	p.Arg203Gln	missense_variant	3/5	ENST00000181796.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM107B	ENST00000181796.7 linkuse as main transcript	c.608G>A	p.Arg203Gln	missense_variant	3/5	2	NM_031453.4		Q9H098-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250892

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135576

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461704

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727150

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 27, 2022

The c.608G>A (p.R203Q) alteration is located in exon 3 (coding exon 3) of the FAM107B gene. This alteration results from a G to A substitution at nucleotide position 608, causing the arginine (R) at amino acid position 203 to be replaced by a glutamine (Q). 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

0.26

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.087

T;T;.;T;T;T;T;T;T;T;T;.;T;T;T;.;T;T;T;T

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.95

.;D;D;.;.;.;.;.;.;.;.;D;D;D;D;D;D;D;D;D

M_CAP

Benign

0.028

MetaRNN

Uncertain

0.58

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.62

MutationAssessor

Uncertain

2.2

M;M;.;M;M;M;M;M;M;M;M;.;.;.;.;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-2.4

N;.;N;N;N;N;N;N;N;N;N;N;N;N;N;D;D;D;D;D

REVEL

Uncertain

0.33

Sift

Benign

0.048

D;.;D;D;D;D;D;D;D;D;D;D;T;T;T;T;T;T;T;D

Sift4G

Benign

0.20

T;T;D;T;T;T;T;T;T;T;T;.;.;.;.;.;T;.;.;.

Polyphen

1.0

D;D;D;D;D;D;D;D;D;D;D;.;.;.;.;.;.;.;.;.

Vest4

0.63

MutPred

0.54

Loss of MoRF binding (P = 0.0147);Loss of MoRF binding (P = 0.0147);.;Loss of MoRF binding (P = 0.0147);Loss of MoRF binding (P = 0.0147);Loss of MoRF binding (P = 0.0147);Loss of MoRF binding (P = 0.0147);Loss of MoRF binding (P = 0.0147);Loss of MoRF binding (P = 0.0147);Loss of MoRF binding (P = 0.0147);Loss of MoRF binding (P = 0.0147);Loss of MoRF binding (P = 0.0147);Loss of MoRF binding (P = 0.0147);Loss of MoRF binding (P = 0.0147);Loss of MoRF binding (P = 0.0147);Loss of MoRF binding (P = 0.0147);Loss of MoRF binding (P = 0.0147);Loss of MoRF binding (P = 0.0147);Loss of MoRF binding (P = 0.0147);Loss of MoRF binding (P = 0.0147);

MVP

0.58

MPC

0.27

ClinPred

0.93

GERP RS

5.2

Varity_R

0.32

gMVP

0.079

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