20-56359069-G-C

Position:

• chr20-56359069-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_080821.3(FAM210B):​c.64G>C​(p.Ala22Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000083 in 1,204,806 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: 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: 0.270

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.095481485).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM210B	NM_080821.3	c.64G>C	p.Ala22Pro	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	c.64G>C	p.Ala22Pro	missense_variant	1/3	1	NM_080821.3	ENSP00000360437	P1
FAM210B	ENST00000437418.1			upstream_gene_variant		3		ENSP00000389768

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.30e-7 AC: 1 AN: 1204806 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 591632

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: 0.00000102

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Sep 20, 2023

The c.64G>C (p.A22P) alteration is located in exon 1 (coding exon 1) of the FAM210B gene. This alteration results from a G to C substitution at nucleotide position 64, causing the alanine (A) at amino acid position 22 to be replaced by a proline (P). 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	0.095
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0072	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
MutationTaster	Benign	1.0	N
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.028
Sift	Benign	0.080	T
Sift4G	Benign	0.19	T
Polyphen		0.0090	B
Vest4		0.24
MutPred		0.34		Gain of loop (P = 0.0079);
MVP		0.13
MPC		0.83
ClinPred		0.099	T
GERP RS		2.5
Varity_R		0.20
gMVP		0.50

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: chr20-54934125;