rs1376731818

Variant names:

• chr5-110528673-T-C
• rs1376731818
• NM_001039763.4:c.1618A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-110528673-T-C
• chr5-110528673-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001039763.4(TMEM232):​c.1618A>G​(p.Lys540Glu) 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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K540Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM232 NM_001039763.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.055624068).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM232	NM_001039763.4	c.1618A>G	p.Lys540Glu	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.1618A>G	p.Lys540Glu	missense_variant	Exon 12 of 14	2	NM_001039763.4	ENSP00000401477.2
TMEM232	ENST00000512003.7	n.*997+39774A>G		intron_variant	Intron 9 of 10	1		ENSP00000427785.2
TMEM232	ENST00000515518.6	n.1375+39774A>G		intron_variant	Intron 10 of 12	1
TMEM232	ENST00000508571.6	n.1018+39774A>G		intron_variant	Intron 5 of 5	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
DANN	Benign	0.92
DEOGEN2	Benign	0.0035	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.7
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.017
Sift	Benign	0.48	T
Sift4G	Benign	0.13	T
Polyphen		0.0020	B
Vest4		0.066
MutPred		0.25		Loss of methylation at K540 (P = 0.004);
MVP		0.014
ClinPred		0.062	T
GERP RS		2.9
Varity_R		0.12
gMVP		0.025
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1376731818; hg19: chr5-109864374;