dbSNP rs200746481: FAM216A:p.Ser53Tyr (chr12-110473092-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_013300.3(FAM216A):c.158C>A(p.Ser53Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000713 in 1,403,152 control chromosomes in the GnomAD database, with no homozygous occurrence. 14/22 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)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

FAM216A
NM_013300.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.231

Publications

0 publications found

Variant links:

Genes affected

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

FAM216A links:

LOC124903016 (HGNC:):

LOC124903016 links:

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ACMG classification

Classification was made for transcript

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.158C>A	p.Ser53Tyr	missense	Exon 2 of 7	NP_037432.2	Q8WUB2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM216A	ENST00000377673.10	TSL:1 MANE Select	c.158C>A	p.Ser53Tyr	missense	Exon 2 of 7	ENSP00000366901.5	Q8WUB2
FAM216A	ENST00000538285.6	TSL:1	n.619C>A		non_coding_transcript_exon	Exon 2 of 5
FAM216A	ENST00000548449.1	TSL:1	n.158C>A		non_coding_transcript_exon	Exon 2 of 4	ENSP00000448777.1	F8VXY8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.13e-7

AC:

AN:

1403152

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

697630

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

32148

American (AMR)

AF:

0.00

AC:

AN:

42320

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24734

East Asian (EAS)

AF:

0.00

AC:

AN:

38884

South Asian (SAS)

AF:

0.00

AC:

AN:

80598

European-Finnish (FIN)

AF:

0.0000194

AC:

AN:

51536

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4350

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1070954

Other (OTH)

AF:

0.00

AC:

AN:

57628

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.070

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

Eigen

Benign

0.050

Eigen_PC

Benign

-0.037

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.72

M_CAP

Benign

0.013

MetaRNN

Uncertain

0.47

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.6

PhyloP100

0.23

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-2.1

REVEL

Benign

0.23

Sift

Benign

0.056

Sift4G

Uncertain

0.021

Polyphen

0.98

Vest4

0.60

MutPred

0.29

Gain of catalytic residue at S49 (P = 0)

MVP

0.50

MPC

0.59

ClinPred

0.81

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.085

gMVP

0.14

Mutation Taster

=87/13

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over