5-110625338-C-G

Position:

• chr5-110625338-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001039763.4(TMEM232):​c.697G>C​(p.Glu233Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000717 in 1,395,386 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 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: 0.0000072 (0 hom.)
• Consequence: TMEM232 NM_001039763.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.87

Genes affected

TMEM232 (HGNC:37270): (transmembrane protein 232) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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=0.16460985).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM232	NM_001039763.4	c.697G>C	p.Glu233Gln	missense_variant	7/14	ENST00000455884.7	NP_001034852.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM232	ENST00000455884.7	c.697G>C	p.Glu233Gln	missense_variant	7/14	2	NM_001039763.4	ENSP00000401477.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000717 AC: 10 AN: 1395386 Hom.: 0 Cov.: 30 AF XY: 0.00000872 AC XY: 6 AN XY: 688106

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: 0.0000127

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000836

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

Feb 17, 2024

The c.697G>C (p.E233Q) alteration is located in exon 7 (coding exon 6) of the TMEM232 gene. This alteration results from a G to C substitution at nucleotide position 697, causing the glutamic acid (E) at amino acid position 233 to be replaced by a glutamine (Q). 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	0.16
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T;.
Eigen	Benign	0.080
Eigen_PC	Benign	0.028
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.3	M;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.035
Sift	Benign	0.066	T;D
Sift4G	Uncertain	0.049	D;.
Polyphen		0.96	D;.
Vest4		0.18
MutPred		0.25		Loss of ubiquitination at K231 (P = 0.0275);Loss of ubiquitination at K231 (P = 0.0275);
MVP		0.048
ClinPred		0.87	D
GERP RS		3.7
Varity_R		0.13
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr5-109961039;