chr5-110605281-G-C

Variant names:

• chr5-110605281-G-C
• rs1286167233
• NM_001039763.4:c.1104C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001039763.4(TMEM232):​c.1104C>G​(p.Ile368Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I368N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: TMEM232 NM_001039763.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.514
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19952497).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039763.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM232	NM_001039763.4	MANE Select	c.1104C>G	p.Ile368Met	missense	Exon 10 of 14	NP_001034852.3	C9JQI7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM232	ENST00000455884.7	TSL:2 MANE Select	c.1104C>G	p.Ile368Met	missense	Exon 10 of 14	ENSP00000401477.2	C9JQI7-1
	TMEM232	ENST00000512003.7	TSL:1	n.*646C>G		non_coding_transcript_exon	Exon 8 of 11	ENSP00000427785.2	E5RG73
	TMEM232	ENST00000515518.6	TSL:1	n.1024C>G		non_coding_transcript_exon	Exon 9 of 13

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399042 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 690060

African (AFR) AF: 0.0000317 AC: 1 AN: 31578

American (AMR) AF: 0.00 AC: 0 AN: 35698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25160

East Asian (EAS) AF: 0.00 AC: 0 AN: 35632

South Asian (SAS) AF: 0.00 AC: 0 AN: 79224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49328

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078724

Other (OTH) AF: 0.00 AC: 0 AN: 58006

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.074	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.087	T
Eigen	Benign	-0.076
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		-0.51
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.16
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.93	P
Vest4		0.41
MutPred		0.24		Loss of catalytic residue at A372 (P = 0.2722)
MVP		0.088
ClinPred		0.94	D
GERP RS		-0.62
Varity_R		0.30
gMVP		0.37
Mutation Taster		=82/18	polymorphism

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

Other links and lift over

dbSNP: rs1286167233; hg19: chr5-109940982;