12-110468885-C-T

Variant names:

• chr12-110468885-C-T
• rs762663066
• NM_013300.3:c.10C>T

Variant summary

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

The NM_013300.3(FAM216A):​c.10C>T​(p.Gln4*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000294 in 1,360,744 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: FAM216A NM_013300.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.352
• Publications: 0 publications found

Genes affected

FAM216A (HGNC:30180): (family with sequence similarity 216 member A)

GPN3 (HGNC:30186): (GPN-loop GTPase 3) Predicted to enable GTPase activity. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013300.3. 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
	FAM216A	NM_013300.3	MANE Select	c.10C>T	p.Gln4*	stop_gained	Exon 1 of 7	NP_037432.2	Q8WUB2
	GPN3	NM_001164372.2		c.-249G>A		upstream_gene	N/A	NP_001157844.1	Q9UHW5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM216A	ENST00000377673.10	TSL:1 MANE Select	c.10C>T	p.Gln4*	stop_gained	Exon 1 of 7	ENSP00000366901.5	Q8WUB2
	FAM216A	ENST00000538285.6	TSL:1	n.471C>T		non_coding_transcript_exon	Exon 1 of 5
	FAM216A	ENST00000548449.1	TSL:1	n.10C>T		non_coding_transcript_exon	Exon 1 of 4	ENSP00000448777.1	F8VXY8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000294 AC: 4 AN: 1360744 Hom.: 0 Cov.: 33 AF XY: 0.00000449 AC XY: 3 AN XY: 668408

African (AFR) AF: 0.00 AC: 0 AN: 30806

American (AMR) AF: 0.00 AC: 0 AN: 32394

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24222

East Asian (EAS) AF: 0.00 AC: 0 AN: 35260

South Asian (SAS) AF: 0.0000129 AC: 1 AN: 77340

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34322

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4964

European-Non Finnish (NFE) AF: 0.00000282 AC: 3 AN: 1064848

Other (OTH) AF: 0.00 AC: 0 AN: 56588

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	27
DANN	Uncertain	0.98
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.0089	N
PhyloP100		-0.35
Vest4		0.083
GERP RS		-1.9
PromoterAI		0.17	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=175/25	disease causing (fs/PTC)

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: rs762663066; hg19: chr12-110906690;