12-110486572-T-C

Variant names:

• chr12-110486572-T-C
• NM_013300.3:c.475T>C

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.475T>C​(p.Tyr159His) 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. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM216A NM_013300.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.988
• 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=0.10915652).

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.475T>C	p.Tyr159His	missense	Exon 5 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.475T>C	p.Tyr159His	missense	Exon 5 of 7	ENSP00000366901.5	Q8WUB2
	FAM216A	ENST00000538285.6	TSL:1	n.936T>C		non_coding_transcript_exon	Exon 5 of 5
	FAM216A	ENST00000548449.1	TSL:1	n.*119T>C		non_coding_transcript_exon	Exon 4 of 4	ENSP00000448777.1	F8VXY8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	14
DANN	Benign	0.95
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.99
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.028
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.020	D
Polyphen		0.0040	B
Vest4		0.23
MutPred		0.25		Gain of catalytic residue at R154 (P = 0.0039)
MVP		0.21
MPC		0.19
ClinPred		0.098	T
GERP RS		0.15
Varity_R		0.13
gMVP		0.094
Mutation Taster		=95/5	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

hg19: chr12-110924377;