12-109768214-C-T

Variant names:

• chr12-109768214-C-T
• rs1889115876
• NM_032829.3:c.285C>T

Variant summary

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

The NM_032829.3(FAM222A):​c.285C>T​(p.His95His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,352 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: FAM222A NM_032829.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.398
• Publications: 0 publications found

Genes affected

FAM222A (HGNC:25915): (family with sequence similarity 222 member A)

FAM222A-AS1 (HGNC:28223): (FAM222A antisense RNA 1)

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=-0.72).
• BP7: Synonymous conserved (PhyloP=-0.398 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032829.3. 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
	FAM222A	NM_032829.3	MANE Select	c.285C>T	p.His95His	synonymous	Exon 3 of 3	NP_116218.2	Q5U5X8
	FAM222A-AS1	NR_026661.2		n.191+5083G>A		intron	N/A
	FAM222A-AS1	NR_026662.2		n.191+5083G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM222A	ENST00000538780.2	TSL:1 MANE Select	c.285C>T	p.His95His	synonymous	Exon 3 of 3	ENSP00000443292.1	Q5U5X8
	FAM222A	ENST00000358906.3	TSL:5	c.285C>T	p.His95His	synonymous	Exon 3 of 3	ENSP00000351783.3	Q5U5X8
	FAM222A	ENST00000898959.1		c.285C>T	p.His95His	synonymous	Exon 2 of 2	ENSP00000569018.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460352 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726418

African (AFR) AF: 0.00 AC: 0 AN: 33432

American (AMR) AF: 0.00 AC: 0 AN: 44644

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39638

South Asian (SAS) AF: 0.00 AC: 0 AN: 86086

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52686

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111650

Other (OTH) AF: 0.00 AC: 0 AN: 60342

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.28
DANN	Benign	0.78
PhyloP100		-0.40

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: rs1889115876; hg19: chr12-110206019;