17-28758457-C-A

Variant names:

• chr17-28758457-C-A
• rs777468977
• NM_001077498.3:c.1502G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001077498.3(FAM222B):​c.1502G>T​(p.Gly501Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,461,164 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: 0.000011 (0 hom.)
• Consequence: FAM222B NM_001077498.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.12
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12280604).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077498.3. 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
	FAM222B	NM_001077498.3	MANE Select	c.1502G>T	p.Gly501Val	missense	Exon 3 of 3	NP_001070966.1	Q8WU58
	FAM222B	NM_001288631.2		c.1508G>T	p.Gly503Val	missense	Exon 4 of 4	NP_001275560.1
	FAM222B	NM_001288632.2		c.1502G>T	p.Gly501Val	missense	Exon 5 of 5	NP_001275561.1	Q8WU58

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM222B	ENST00000581407.6	TSL:1 MANE Select	c.1502G>T	p.Gly501Val	missense	Exon 3 of 3	ENSP00000462419.1	Q8WU58
	FAM222B	ENST00000582266.6	TSL:1	c.*1303G>T		3_prime_UTR	Exon 3 of 3	ENSP00000462534.1	J3KSK8
	FAM222B	ENST00000452648.8	TSL:2	c.1502G>T	p.Gly501Val	missense	Exon 3 of 3	ENSP00000413645.3	Q8WU58

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000161 AC: 4 AN: 248270 AF XY: 0.0000223

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000267

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.0000110 AC: 16 AN: 1461164 Hom.: 0 Cov.: 30 AF XY: 0.0000124 AC XY: 9 AN XY: 726846

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53136

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.00000989 AC: 11 AN: 1111704

Other (OTH) AF: 0.0000331 AC: 2 AN: 60366

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000283 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000827 AC: 1

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	0.086
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.065
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.1
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.038
Sift	Uncertain	0.011	D
Sift4G	Benign	0.064	T
Polyphen		0.017	B
Vest4		0.28
MutPred		0.59		Loss of disorder (P = 0.0446)
MVP		0.043
MPC		0.15
ClinPred		0.18	T
GERP RS		3.7
Varity_R		0.25
gMVP		0.46
Mutation Taster		=77/23	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

dbSNP: rs777468977; hg19: chr17-27085475;