Variant 2-24177869-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001040710.3(FAM228A):c.161A>G(p.Lys54Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000394 in 1,600,730 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/25 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00039 ( 2 hom. )

Consequence

FAM228A
NM_001040710.3 missense, splice_region

Scores

Splicing: ADA: 0.2648

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.75

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17646089).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM228A	NM_001040710.3 link	c.161A>G	p.Lys54Arg	missense_variant, splice_region_variant	3/6	ENST00000295150.8	NP_001035800.1	Q86W67

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FAM228A	ENST00000295150.8 link	c.161A>G	p.Lys54Arg	missense_variant, splice_region_variant	3/6	1	NM_001040710.3	ENSP00000295150.3	Q86W67
ENSG00000276087	ENST00000610442.1 link	n.*1288A>G		splice_region_variant, non_coding_transcript_exon_variant	11/14	2		ENSP00000483650.1	A0A087X0T9
ENSG00000276087	ENST00000610442.1 link	n.*1288A>G		3_prime_UTR_variant	11/14	2		ENSP00000483650.1	A0A087X0T9

Frequencies

GnomAD3 genomes

AF:

0.000394

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000823

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000281

AC:

AN:

245762

Hom.:

AF XY:

0.000270

AC XY:

AN XY:

133414

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000399

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000338

Gnomad FIN exome

AF:

0.0000468

Gnomad NFE exome

AF:

0.000533

Gnomad OTH exome

AF:

0.000504

GnomAD4 exome

AF:

0.000394

AC:

570

AN:

1448500

Hom.:

Cov.:

AF XY:

0.000413

AC XY:

298

AN XY:

721196

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000307

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.000132

Gnomad4 NFE exome

AF:

0.000488

Gnomad4 OTH exome

AF:

0.000250

GnomAD4 genome

AF:

0.000394

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000823

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000562

Hom.:

Bravo

AF:

0.000314

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000484

AC:

ExAC

AF:

0.000372

AC:

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

Nov 11, 2024

The c.161A>G (p.K54R) alteration is located in exon 3 (coding exon 2) of the FAM228A gene. This alteration results from a A to G substitution at nucleotide position 161, causing the lysine (K) at amino acid position 54 to be replaced by an arginine (R). 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

0.14

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

Eigen

Benign

0.18

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.43

M_CAP

Benign

0.013

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.1

PrimateAI

Benign

0.46

PROVEAN

Benign

-2.3

REVEL

Benign

0.25

Sift

Benign

0.083

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.38

MVP

0.27

MPC

0.29

ClinPred

0.12

GERP RS

3.1

Varity_R

0.096

gMVP

0.062

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.26

dbscSNV1_RF

Benign

0.44

SpliceAI score (max)

0.37

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.37

Position offset: 1

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