20-56359022-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_080821.3(FAM210B):​c.17C>T​(p.Ala6Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000247 in 1,337,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

FAM210B
NM_080821.3 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.69
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06307536).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FAM210BNM_080821.3 linkuse as main transcriptc.17C>T p.Ala6Val missense_variant 1/3 ENST00000371384.4 NP_543011.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FAM210BENST00000371384.4 linkuse as main transcriptc.17C>T p.Ala6Val missense_variant 1/31 NM_080821.3 ENSP00000360437 P1

Frequencies

GnomAD3 genomes
AF:
0.00000663
AC:
1
AN:
150818
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000148
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000270
AC:
32
AN:
1187000
Hom.:
0
Cov.:
31
AF XY:
0.0000257
AC XY:
15
AN XY:
582652
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
0.0000330
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000663
AC:
1
AN:
150818
Hom.:
0
Cov.:
32
AF XY:
0.0000136
AC XY:
1
AN XY:
73620
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000148
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151

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 submitterclinical testingAmbry GeneticsAug 02, 2022The c.17C>T (p.A6V) alteration is located in exon 1 (coding exon 1) of the FAM210B gene. This alteration results from a C to T substitution at nucleotide position 17, causing the alanine (A) at amino acid position 6 to be replaced by a valine (V). 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
0.19
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
7.2
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0085
T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.034
N
LIST_S2
Benign
0.46
T
M_CAP
Benign
0.064
D
MetaRNN
Benign
0.063
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
1.3
L
MutationTaster
Benign
1.0
N
PrimateAI
Pathogenic
0.80
T
PROVEAN
Benign
-0.85
N
REVEL
Benign
0.025
Sift
Uncertain
0.023
D
Sift4G
Benign
0.29
T
Polyphen
0.079
B
Vest4
0.074
MutPred
0.29
Loss of helix (P = 0.0237);
MVP
0.030
MPC
0.45
ClinPred
0.082
T
GERP RS
-0.89
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.050
gMVP
0.40

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.

Other links and lift over

dbSNP: rs1010505617; hg19: chr20-54934078; API