20-56366109-T-A

Position:

• chr20-56366109-T-A

Variant summary

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

The NM_080821.3(FAM210B):​c.401T>A​(p.Phe134Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FAM210B NM_080821.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.61

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

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	Protein	UniProt
FAM210B	NM_080821.3	c.401T>A	p.Phe134Tyr	missense_variant	3/3	ENST00000371384.4	NP_543011.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM210B	ENST00000371384.4	c.401T>A	p.Phe134Tyr	missense_variant	3/3	1	NM_080821.3	ENSP00000360437	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2023

The c.401T>A (p.F134Y) alteration is located in exon 3 (coding exon 3) of the FAM210B gene. This alteration results from a T to A substitution at nucleotide position 401, causing the phenylalanine (F) at amino acid position 134 to be replaced by a tyrosine (Y). 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	Uncertain	0.38
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T
Eigen	Uncertain	0.33
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.2	M
MutationTaster	Benign	0.95	N
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.24
Sift	Benign	0.036	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.98	D
Vest4		0.46
MutPred		0.56		Loss of methylation at K135 (P = 0.0401);
MVP		0.26
MPC		1.4
ClinPred		0.92	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.25
gMVP		0.80

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-54941165;