chr20-56359060-C-T

Variant names:

• chr20-56359060-C-T
• NM_080821.3:c.55C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_080821.3(FAM210B):​c.55C>T​(p.Arg19Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000831 in 1,203,154 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.3e-7 (0 hom.)
• Consequence: FAM210B NM_080821.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.282
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28966683).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080821.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM210B	NM_080821.3	MANE Select	c.55C>T	p.Arg19Trp	missense	Exon 1 of 3	NP_543011.2	Q96KR6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM210B	ENST00000371384.4	TSL:1 MANE Select	c.55C>T	p.Arg19Trp	missense	Exon 1 of 3	ENSP00000360437.3	Q96KR6
	FAM210B	ENST00000437418.1	TSL:3	c.-51C>T		upstream_gene	N/A	ENSP00000389768.1	H0Y456

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.31e-7 AC: 1 AN: 1203154 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 590988

African (AFR) AF: 0.00 AC: 0 AN: 24342

American (AMR) AF: 0.00 AC: 0 AN: 19842

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18540

East Asian (EAS) AF: 0.00 AC: 0 AN: 24436

South Asian (SAS) AF: 0.00 AC: 0 AN: 56750

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27802

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3288

European-Non Finnish (NFE) AF: 0.00000102 AC: 1 AN: 980550

Other (OTH) AF: 0.00 AC: 0 AN: 47604

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.81	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.28
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.15
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.31
MutPred		0.46		Loss of disorder (P = 0.0012)
MVP		0.33
MPC		0.46
ClinPred		0.88	D
GERP RS		0.29
PromoterAI		-0.012	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.15
gMVP		0.40
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

hg19: chr20-54934116; COSMIC: COSV105298542; COSMIC: COSV105298542;