5-110528795-C-T

Variant names:

• chr5-110528795-C-T
• NM_001039763.4:c.1496G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001039763.4(TMEM232):​c.1496G>A​(p.Ser499Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/19 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)
• Consequence: TMEM232 NM_001039763.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.668

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 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=0.046114355).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM232	NM_001039763.4	c.1496G>A	p.Ser499Asn	missense_variant	Exon 12 of 14	ENST00000455884.7	NP_001034852.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM232	ENST00000455884.7	c.1496G>A	p.Ser499Asn	missense_variant	Exon 12 of 14	2	NM_001039763.4	ENSP00000401477.2
TMEM232	ENST00000512003.7	n.*997+39652G>A		intron_variant	Intron 9 of 10	1		ENSP00000427785.2
TMEM232	ENST00000515518.6	n.1375+39652G>A		intron_variant	Intron 10 of 12	1
TMEM232	ENST00000508571.6	n.1018+39652G>A		intron_variant	Intron 5 of 5	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 27, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1496G>A (p.S499N) alteration is located in exon 12 (coding exon 11) of the TMEM232 gene. This alteration results from a G to A substitution at nucleotide position 1496, causing the serine (S) at amino acid position 499 to be replaced by an asparagine (N). 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	0.084
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.57
DANN	Benign	0.22
DEOGEN2	Benign	0.0038	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.83	N
REVEL	Benign	0.012
Sift	Benign	0.40	T
Sift4G	Benign	0.15	T
Polyphen		0.0040	B
Vest4		0.0090
MutPred		0.20		Loss of phosphorylation at S499 (P = 0.0508);
MVP		0.014
ClinPred		0.021	T
GERP RS		-0.62
Varity_R		0.060
gMVP		0.040

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr5-109864496;