12-110473092-C-G

Variant names:

• chr12-110473092-C-G
• rs200746481
• NM_013300.3:c.158C>G

Variant summary

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

The NM_013300.3(FAM216A):​c.158C>G​(p.Ser53Cys) variant causes a missense 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. 15/22 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. S53F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FAM216A NM_013300.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.231
• Publications: 0 publications found

Genes affected

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

LOC124903016 (HGNC:):

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=0.072707444).

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.158C>G	p.Ser53Cys	missense	Exon 2 of 7	NP_037432.2	Q8WUB2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM216A	ENST00000377673.10	TSL:1 MANE Select	c.158C>G	p.Ser53Cys	missense	Exon 2 of 7	ENSP00000366901.5	Q8WUB2
	FAM216A	ENST00000538285.6	TSL:1	n.619C>G		non_coding_transcript_exon	Exon 2 of 5
	FAM216A	ENST00000548449.1	TSL:1	n.158C>G		non_coding_transcript_exon	Exon 2 of 4	ENSP00000448777.1	F8VXY8

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 23

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.95	L
PhyloP100		0.23
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.021
Sift	Benign	0.089	T
Sift4G	Benign	0.12	T
Polyphen		0.019	B
Vest4		0.38
MutPred		0.33		Gain of catalytic residue at S49 (P = 0)
MVP		0.27
MPC		0.14
ClinPred		0.071	T
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.096
gMVP		0.11
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs200746481; hg19: chr12-110910897;