Variant 2-24175563-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001040710.3(FAM228A):c.83C>G(p.Ser28Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 1,613,280 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

FAM228A
NM_001040710.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.480

Variant links:

Genes affected

FAM228A (HGNC:34418): (family with sequence similarity 228 member A)

FAM228A links:

ENSG00000276087 (HGNC:):

ENSG00000276087 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=0.22189006).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM228A	NM_001040710.3 linkuse as main transcript	c.83C>G	p.Ser28Cys	missense_variant	2/6	ENST00000295150.8	NP_001035800.1	Q86W67

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FAM228A	ENST00000295150.8 linkuse as main transcript	c.83C>G	p.Ser28Cys	missense_variant	2/6	1	NM_001040710.3	ENSP00000295150.3	Q86W67
ENSG00000276087	ENST00000610442.1 linkuse as main transcript	n.*996C>G		non_coding_transcript_exon_variant	9/14	2		ENSP00000483650.1	A0A087X0T9
ENSG00000276087	ENST00000610442.1 linkuse as main transcript	n.*996C>G		3_prime_UTR_variant	9/14	2		ENSP00000483650.1	A0A087X0T9

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

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:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000240

AC:

AN:

249558

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135398

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000530

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000119

AC:

174

AN:

1461044

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

726920

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000154

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0000482

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:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000847

Hom.:

Bravo

AF:

0.0000793

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000248

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 29, 2022

The c.83C>G (p.S28C) alteration is located in exon 2 (coding exon 1) of the FAM228A gene. This alteration results from a C to G substitution at nucleotide position 83, causing the serine (S) at amino acid position 28 to be replaced by a cysteine (C). 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

0.13

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.033

Eigen

Benign

-0.038

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.62

M_CAP

Benign

0.013

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.1

PrimateAI

Benign

0.36

PROVEAN

Benign

-2.0

REVEL

Benign

0.15

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.010

Polyphen

1.0

Vest4

0.29

MutPred

0.46

Loss of disorder (P = 0.0067);

MVP

0.40

MPC

0.33

ClinPred

0.36

GERP RS

3.8

Varity_R

0.14

gMVP

0.024

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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