rs369987412

Variant names:

• chr17-28758956-C-A
• rs369987412
• NM_001077498.3:c.1003G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-28758956-C-A
• chr17-28758956-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001077498.3(FAM222B):​c.1003G>T​(p.Ala335Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,458,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A335T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: FAM222B NM_001077498.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.13
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16012084).

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.1003G>T	p.Ala335Ser	missense	Exon 3 of 3	NP_001070966.1	Q8WU58
	FAM222B	NM_001288631.2		c.1009G>T	p.Ala337Ser	missense	Exon 4 of 4	NP_001275560.1
	FAM222B	NM_001288632.2		c.1003G>T	p.Ala335Ser	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.1003G>T	p.Ala335Ser	missense	Exon 3 of 3	ENSP00000462419.1	Q8WU58
	FAM222B	ENST00000582266.6	TSL:1	c.*804G>T		3_prime_UTR	Exon 3 of 3	ENSP00000462534.1	J3KSK8
	FAM222B	ENST00000452648.8	TSL:2	c.1003G>T	p.Ala335Ser	missense	Exon 3 of 3	ENSP00000413645.3	Q8WU58

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1458010 Hom.: 0 Cov.: 33 AF XY: 0.00000276 AC XY: 2 AN XY: 724964

African (AFR) AF: 0.00 AC: 0 AN: 33430

American (AMR) AF: 0.00 AC: 0 AN: 44018

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25962

East Asian (EAS) AF: 0.00 AC: 0 AN: 39582

South Asian (SAS) AF: 0.00 AC: 0 AN: 85498

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53006

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1110532

Other (OTH) AF: 0.00 AC: 0 AN: 60222

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Benign	0.89
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		3.1
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.036
Sift	Benign	0.067	T
Sift4G	Benign	0.17	T
Polyphen		0.24	B
Vest4		0.31
MutPred		0.24		Gain of glycosylation at A335 (P = 0.0019)
MVP		0.068
MPC		0.11
ClinPred		0.41	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.30
Mutation Taster		=84/16	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: rs369987412; hg19: chr17-27085974; COSMIC: COSV57933398; COSMIC: COSV57933398;