17-28758546-A-T

Variant names:

• chr17-28758546-A-T
• rs2043031
• NM_001077498.3:c.1413T>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001077498.3(FAM222B):​c.1413T>A​(p.Leu471Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM222B NM_001077498.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.370
• Publications: 21 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=-0.37 with no splicing effect.

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.1413T>A	p.Leu471Leu	synonymous	Exon 3 of 3	NP_001070966.1	Q8WU58
	FAM222B	NM_001288631.2		c.1419T>A	p.Leu473Leu	synonymous	Exon 4 of 4	NP_001275560.1
	FAM222B	NM_001288632.2		c.1413T>A	p.Leu471Leu	synonymous	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.1413T>A	p.Leu471Leu	synonymous	Exon 3 of 3	ENSP00000462419.1	Q8WU58
	FAM222B	ENST00000582266.6	TSL:1	c.*1214T>A		3_prime_UTR	Exon 3 of 3	ENSP00000462534.1	J3KSK8
	FAM222B	ENST00000452648.8	TSL:2	c.1413T>A	p.Leu471Leu	synonymous	Exon 3 of 3	ENSP00000413645.3	Q8WU58

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.3
DANN	Benign	0.60
PhyloP100		-0.37

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: rs2043031; hg19: chr17-27085564;