17-28758424-T-G

Variant names:

• chr17-28758424-T-G
• NM_001077498.3:c.1535A>C

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 rank	MANE	Protein	UniProt
FAM222B	NM_001077498.3	c.1535A>C	p.Gln512Pro	missense_variant	Exon 3 of 3	ENST00000581407.6	NP_001070966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM222B	ENST00000581407.6	c.1535A>C	p.Gln512Pro	missense_variant	Exon 3 of 3	1	NM_001077498.3	ENSP00000462419.1

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

Dec 19, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
DEOGEN2	Benign	0.24	.;T;T
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
MutationAssessor	Benign	1.8	.;L;L
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-3.8	.;.;D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0020	.;.;D
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;