Variant 2-24183499-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001040710.3(FAM228A):c.255A>T(p.Lys85Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000224 in 1,610,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

FAM228A
NM_001040710.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.913

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34148002).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM228A	NM_001040710.3 linkuse as main transcript	c.255A>T	p.Lys85Asn	missense_variant	5/6	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.255A>T	p.Lys85Asn	missense_variant	5/6	1	NM_001040710.3	ENSP00000295150.3	Q86W67
ENSG00000276087	ENST00000610442.1 linkuse as main transcript	n.*1382A>T		non_coding_transcript_exon_variant	13/14	2		ENSP00000483650.1	A0A087X0T9
ENSG00000276087	ENST00000610442.1 linkuse as main transcript	n.*1382A>T		3_prime_UTR_variant	13/14	2		ENSP00000483650.1	A0A087X0T9

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000814

AC:

AN:

245700

Hom.:

AF XY:

0.00000751

AC XY:

AN XY:

133192

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000297

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:

0.00000892

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000226

AC:

AN:

1457976

Hom.:

Cov.:

AF XY:

0.0000221

AC XY:

AN XY:

724902

show subpopulations

Gnomad4 AFR exome

AF:

0.000331

Gnomad4 AMR exome

AF:

0.0000228

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:

0.00000720

Gnomad4 OTH exome

AF:

0.000183

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.0000331

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Mar 30, 2024

The c.255A>T (p.K85N) alteration is located in exon 5 (coding exon 4) of the FAM228A gene. This alteration results from a A to T substitution at nucleotide position 255, causing the lysine (K) at amino acid position 85 to be replaced by an asparagine (N). 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

Pathogenic

0.58

BayesDel_addAF

Benign

-0.077

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.72

M_CAP

Benign

0.025

MetaRNN

Benign

0.34

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.5

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-3.9

REVEL

Benign

0.081

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.39

MutPred

0.23

Loss of solvent accessibility (P = 0.0079);

MVP

0.40

MPC

0.36

ClinPred

0.93

GERP RS

0.91

Varity_R

0.36

gMVP

0.029

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

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