Variant 20-56359187-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_080821.3(FAM210B):c.182A>G(p.His61Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000518 in 1,235,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

FAM210B
NM_080821.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0440

Variant links:

Genes affected

FAM210B (HGNC:16102): (family with sequence similarity 210 member B) Involved in cellular response to estradiol stimulus and positive regulation of erythrocyte differentiation. Located in mitochondrial outer membrane. Is intrinsic component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

FAM210B links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.017158478).

BP6

Variant 20-56359187-A-G is Benign according to our data. Variant chr20-56359187-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3092269.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM210B	NM_080821.3 linkuse as main transcript	c.182A>G	p.His61Arg	missense_variant	1/3	ENST00000371384.4	NP_543011.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM210B	ENST00000371384.4 linkuse as main transcript	c.182A>G	p.His61Arg	missense_variant	1/3	1	NM_080821.3	ENSP00000360437	P1
FAM210B	ENST00000437418.1 linkuse as main transcript	c.80A>G	p.His27Arg	missense_variant	1/2	3		ENSP00000389768

Frequencies

GnomAD3 genomes

AF:

0.000329

AC:

AN:

151988

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000129

AC:

AN:

1083074

Hom.:

Cov.:

AF XY:

0.00000971

AC XY:

AN XY:

514740

show subpopulations

Gnomad4 AFR exome

AF:

0.000621

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000329

AC:

AN:

151988

Hom.:

Cov.:

AF XY:

0.000337

AC XY:

AN XY:

74220

show subpopulations

Gnomad4 AFR

AF:

0.00121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000348

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 09, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.66

CADD

Benign

1.5

DANN

Benign

0.48

DEOGEN2

Benign

0.0025

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0043

LIST_S2

Benign

0.26

M_CAP

Benign

0.0084

MetaRNN

Benign

0.017

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.79

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.50

PROVEAN

Benign

0.060

REVEL

Benign

0.036

Sift

Benign

1.0

Sift4G

Benign

0.65

Polyphen

0.0010

Vest4

0.052

MutPred

0.20

Gain of MoRF binding (P = 0.0249);

MVP

0.055

MPC

0.55

ClinPred

0.037

GERP RS

-5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.029

gMVP

0.099

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