17-28758424-T-G

Variant summary

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

The NM_001077498.3(FAM222B):c.1535A>C(p.Gln512Pro) 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: 32)
• Consequence: FAM222B NM_001077498.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.56

Genes affected

FAM222B (HGNC:25563): (family with sequence similarity 222 member B) Located in nucleoplasm. [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	UniProt
FAM222B	NM_001077498.3	c.1535A>C	p.Gln512Pro	missense_variant	3/3	ENST00000581407.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM222B	ENST00000581407.6	c.1535A>C	p.Gln512Pro	missense_variant	3/3	1	NM_001077498.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Dec 19, 2022

The c.1535A>C (p.Q512P) alteration is located in exon 4 (coding exon 2) of the FAM222B gene. This alteration results from a A to C substitution at nucleotide position 1535, causing the glutamine (Q) at amino acid position 512 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	0.10
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
Cadd	Benign	21
Dann	Uncertain	0.98
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.81	T;.;T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.55	D;D;D
MetaSVM	Benign	-0.84	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.74	T
REVEL	Uncertain	0.38
Sift4G	Benign	0.11	T;T;T
Polyphen		1.0	.;D;D
Vest4		0.63
MutPred		0.60		.;Gain of glycosylation at T513 (P = 0.0383);Gain of glycosylation at T513 (P = 0.0383);
MVP		0.18
MPC		0.15
ClinPred		0.88	D
GERP RS		3.7
Varity_R		0.84
gMVP		0.77

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: chr17-27085442;