5-110528750-T-C

Position:

• chr5-110528750-T-C

Variant summary

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

The NM_001039763.4(TMEM232):​c.1541A>G​(p.Tyr514Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,382,198 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TMEM232 NM_001039763.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.71

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM232	NM_001039763.4	c.1541A>G	p.Tyr514Cys	missense_variant	12/14	ENST00000455884.7	NP_001034852.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM232	ENST00000455884.7	c.1541A>G	p.Tyr514Cys	missense_variant	12/14	2	NM_001039763.4	ENSP00000401477	P1
TMEM232	ENST00000512003.7	c.*997+39697A>G		intron_variant, NMD_transcript_variant		1		ENSP00000427785
TMEM232	ENST00000515518.6	n.1375+39697A>G		intron_variant, non_coding_transcript_variant		1
TMEM232	ENST00000508571.6	n.1018+39697A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1382198 Hom.: 0 Cov.: 31 AF XY: 0.00000293 AC XY: 2 AN XY: 682042

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: 0.00000186

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 06, 2023

The c.1541A>G (p.Y514C) alteration is located in exon 12 (coding exon 11) of the TMEM232 gene. This alteration results from a A to G substitution at nucleotide position 1541, causing the tyrosine (Y) at amino acid position 514 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	0.18
BayesDel_addAF	Uncertain	0.025	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.051	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	2.0	M
MutationTaster	Benign	1.0	D;N
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.21
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.57
MutPred		0.34		Gain of methylation at K513 (P = 0.0312);
MVP		0.14
ClinPred		0.97	D
GERP RS		4.0
Varity_R		0.19
gMVP		0.12

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

Other links and lift over

dbSNP: rs1194186106; hg19: chr5-109864451;