Genetic Variant FAM216A:p.Ser53Phe (chr12-110473092-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_013300.3(FAM216A):c.158C>T(p.Ser53Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000953 in 1,553,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

FAM216A
NM_013300.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.231

Variant links:

Genes affected

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

FAM216A links:

LOC124903016 (HGNC:):

LOC124903016 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14211369).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM216A	NM_013300.3 link	c.158C>T	p.Ser53Phe	missense_variant	Exon 2 of 7	ENST00000377673.10	NP_037432.2	Q8WUB2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FAM216A	ENST00000377673.10 link	c.158C>T	p.Ser53Phe	missense_variant	Exon 2 of 7	1	NM_013300.3	ENSP00000366901.5	Q8WUB2
FAM216A	ENST00000538285.6 link	n.619C>T		non_coding_transcript_exon_variant	Exon 2 of 5	1
FAM216A	ENST00000548449.1 link	n.158C>T		non_coding_transcript_exon_variant	Exon 2 of 4	1		ENSP00000448777.1	F8VXY8
FAM216A	ENST00000548869.1 link	n.117C>T		non_coding_transcript_exon_variant	Exon 2 of 5	2

Frequencies

GnomAD3 genomes

AF:

0.0000531

AC:

AN:

150540

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000691

AC:

AN:

231482

Hom.:

AF XY:

0.0000718

AC XY:

AN XY:

125300

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000620

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000135

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000998

AC:

140

AN:

1403136

Hom.:

Cov.:

AF XY:

0.000103

AC XY:

AN XY:

697622

show subpopulations

Gnomad4 AFR exome

AF:

0.0000311

Gnomad4 AMR exome

AF:

0.0000473

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000124

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000120

Gnomad4 OTH exome

AF:

0.000121

GnomAD4 genome

AF:

0.0000531

AC:

AN:

150540

Hom.:

Cov.:

AF XY:

0.0000409

AC XY:

AN XY:

73276

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000135

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000825

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.158C>T (p.S53F) alteration is located in exon 2 (coding exon 2) of the FAM216A gene. This alteration results from a C to T substitution at nucleotide position 158, causing the serine (S) at amino acid position 53 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.099

Eigen

Benign

0.026

Eigen_PC

Benign

-0.055

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.66

M_CAP

Benign

0.014

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.6

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-2.0

REVEL

Benign

0.20

Sift

Benign

0.086

Sift4G

Uncertain

0.021

Polyphen

0.98

Vest4

0.34

MutPred

0.33

Gain of catalytic residue at S49 (P = 0);

MVP

0.50

MPC

0.45

ClinPred

0.22

GERP RS

2.0

Varity_R

0.086

gMVP

0.13

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over