Variant 2-24190563-G-T 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.553G>T(p.Gly185Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000327 in 1,612,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00034 ( 0 hom. )

Consequence

FAM228A
NM_001040710.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.38

Variant links:

Genes affected

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

FAM228A 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=0.11562434).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM228A	NM_001040710.3 linkuse as main transcript	c.553G>T	p.Gly185Cys	missense_variant	6/6	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.553G>T	p.Gly185Cys	missense_variant	6/6	1	NM_001040710.3	ENSP00000295150.3	Q86W67
FAM228A	ENST00000432434.2 linkuse as main transcript	c.660+10G>T		intron_variant		5		ENSP00000412833.2	H7C3M9
FAM228A	ENST00000415196.1 linkuse as main transcript	c.246+10G>T		intron_variant		2		ENSP00000416595.1	H7C4B8
FAM228A	ENST00000456591.6 linkuse as main transcript	n.*409+10G>T		intron_variant		3		ENSP00000401257.1	F2Z3J0

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000367

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000157

AC:

AN:

247690

Hom.:

AF XY:

0.000179

AC XY:

AN XY:

134380

show subpopulations

Gnomad AFR exome

AF:

0.000130

Gnomad AMR exome

AF:

0.0000294

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000132

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000284

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000341

AC:

498

AN:

1460280

Hom.:

Cov.:

AF XY:

0.000324

AC XY:

235

AN XY:

726428

show subpopulations

Gnomad4 AFR exome

AF:

0.0000601

Gnomad4 AMR exome

AF:

0.0000451

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000419

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.000197

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000131

Hom.:

Bravo

AF:

0.000181

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000121

AC:

ExAC

AF:

0.000124

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000415

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

Aug 12, 2021

The c.553G>T (p.G185C) alteration is located in exon 6 (coding exon 5) of the FAM228A gene. This alteration results from a G to T substitution at nucleotide position 553, causing the glycine (G) at amino acid position 185 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

0.12

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.024

Eigen

Benign

-0.094

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.083

LIST_S2

Benign

0.27

M_CAP

Benign

0.031

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.83

MutationAssessor

Benign

0.34

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.8

REVEL

Benign

0.15

Sift

Uncertain

0.012

Sift4G

Uncertain

0.019

Polyphen

1.0

Vest4

0.17

MVP

0.50

MPC

0.29

ClinPred

0.094

GERP RS

3.4

Varity_R

0.16

gMVP

0.011

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