Variant chr7-124032342-C-A 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_001136002.2(TMEM229A):c.662G>T(p.Arg221Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000172 in 1,542,284 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

TMEM229A
NM_001136002.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.138

Variant links:

Genes affected

TMEM229A (HGNC:37279): (transmembrane protein 229A) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM229A links:

ENSG00000242593 (HGNC:):

ENSG00000242593 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=0.15675804).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM229A	NM_001136002.2 linkuse as main transcript	c.662G>T	p.Arg221Leu	missense_variant	1/1	ENST00000455783.3	NP_001129474.1	B2RXF0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TMEM229A	ENST00000455783.3 linkuse as main transcript	c.662G>T	p.Arg221Leu	missense_variant	1/1	6	NM_001136002.2	ENSP00000395244.1	B2RXF0
ENSG00000242593	ENST00000484322.5 linkuse as main transcript	n.75+63C>A		intron_variant		1
ENSG00000242593	ENST00000660727.1 linkuse as main transcript	n.128+63C>A		intron_variant
ENSG00000242593	ENST00000667657.1 linkuse as main transcript	n.154+63C>A		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000104

AC:

AN:

135186

Hom.:

AF XY:

0.0000955

AC XY:

AN XY:

73282

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000846

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:

0.000250

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000175

AC:

243

AN:

1389996

Hom.:

Cov.:

AF XY:

0.000155

AC XY:

106

AN XY:

685192

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000859

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:

0.000218

Gnomad4 OTH exome

AF:

0.000104

GnomAD4 genome

AF:

0.000144

AC:

AN:

152288

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000175

Hom.:

Bravo

AF:

0.000121

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000377

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 06, 2023

The c.662G>T (p.R221L) alteration is located in exon 1 (coding exon 1) of the TMEM229A gene. This alteration results from a G to T substitution at nucleotide position 662, causing the arginine (R) at amino acid position 221 to be replaced by a leucine (L). 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

-0.27

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0027

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.60

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

0.12

REVEL

Benign

0.12

Sift

Benign

0.11

Sift4G

Uncertain

0.023

Polyphen

1.0

Vest4

0.24

MVP

0.12

ClinPred

0.28

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.31

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