Variant chr7-124032375-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001136002.2(TMEM229A):c.629G>A(p.Gly210Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,389,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TMEM229A
NM_001136002.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.228

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.046297103).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM229A	NM_001136002.2 linkuse as main transcript	c.629G>A	p.Gly210Asp	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.629G>A	p.Gly210Asp	missense_variant	1/1	6	NM_001136002.2	ENSP00000395244.1	B2RXF0
ENSG00000242593	ENST00000484322.5 linkuse as main transcript	n.75+96C>T		intron_variant		1
ENSG00000242593	ENST00000660727.1 linkuse as main transcript	n.128+96C>T		intron_variant
ENSG00000242593	ENST00000667657.1 linkuse as main transcript	n.154+96C>T		intron_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000760

AC:

AN:

131556

Hom.:

AF XY:

0.0000139

AC XY:

AN XY:

71766

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:

0.00

Gnomad OTH exome

AF:

0.000258

GnomAD4 exome

AF:

0.00000144

AC:

AN:

1389114

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

684866

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000284

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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

Dec 01, 2022

The c.629G>A (p.G210D) alteration is located in exon 1 (coding exon 1) of the TMEM229A gene. This alteration results from a G to A substitution at nucleotide position 629, causing the glycine (G) at amino acid position 210 to be replaced by an aspartic acid (D). 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

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

5.5

DANN

Benign

0.85

DEOGEN2

Benign

0.0044

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.35

M_CAP

Benign

0.043

MetaRNN

Benign

0.046

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.49

REVEL

Benign

0.010

Sift

Benign

0.52

Sift4G

Benign

0.18

Polyphen

0.0010

Vest4

0.11

MutPred

0.17

Loss of methylation at R212 (P = 0.0536);

MVP

0.030

ClinPred

0.036

GERP RS

-4.5

Varity_R

0.047

gMVP

0.25

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