7-124032268-A-G

Position:

• chr7-124032268-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001136002.2(TMEM229A):​c.736T>C​(p.Phe246Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000715 in 1,399,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: TMEM229A NM_001136002.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.80

Genes affected

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

ENSG00000242593 (HGNC:):

ACMG classification

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=0.31153178).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM229A	NM_001136002.2	c.736T>C	p.Phe246Leu	missense_variant	1/1	ENST00000455783.3	NP_001129474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM229A	ENST00000455783.3	c.736T>C	p.Phe246Leu	missense_variant	1/1	6	NM_001136002.2	ENSP00000395244.1
ENSG00000242593	ENST00000484322.5	n.64A>G		non_coding_transcript_exon_variant	1/9	1
ENSG00000242593	ENST00000660727.1	n.117A>G		non_coding_transcript_exon_variant	1/9
ENSG00000242593	ENST00000667657.1	n.143A>G		non_coding_transcript_exon_variant	1/10

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399152 Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1 AN XY: 690054

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 01, 2022

The c.736T>C (p.F246L) alteration is located in exon 1 (coding exon 1) of the TMEM229A gene. This alteration results from a T to C substitution at nucleotide position 736, causing the phenylalanine (F) at amino acid position 246 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	Pathogenic	0.95
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0013	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.87	L
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.13
Sift	Benign	0.29	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.33
MutPred		0.19		Gain of disorder (P = 0.2233);
MVP		0.41
ClinPred		0.96	D
GERP RS		5.4
Varity_R		0.15
gMVP		0.77

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-123672322;