rs371103290

Variant names:

• chr5-110420594-T-C
• rs371103290
• NM_001039763.4:c.1960A>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.1960A>G​(p.Lys654Glu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMEM232 NM_001039763.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0350
• 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: 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=0.043476522).

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.1960A>G	p.Lys654Glu	missense	Exon 14 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.1960A>G	p.Lys654Glu	missense	Exon 14 of 14	ENSP00000401477.2	C9JQI7-1
	TMEM232	ENST00000512003.7	TSL:1	n.*1254A>G		non_coding_transcript_exon	Exon 11 of 11	ENSP00000427785.2	E5RG73
	TMEM232	ENST00000515518.6	TSL:1	n.1632A>G		non_coding_transcript_exon	Exon 12 of 13

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1311490 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 645752

African (AFR) AF: 0.00 AC: 0 AN: 26354

American (AMR) AF: 0.00 AC: 0 AN: 16734

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22566

East Asian (EAS) AF: 0.00 AC: 0 AN: 31792

South Asian (SAS) AF: 0.00 AC: 0 AN: 66172

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33056

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5308

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1054852

Other (OTH) AF: 0.00 AC: 0 AN: 54656

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3476

ClinVar

ClinVar submissions as Germline

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	0.069
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	2.3
DANN	Benign	0.91
DEOGEN2	Benign	0.00097	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.070	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.55	N
PhyloP100		-0.035
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.10	N
REVEL	Benign	0.037
Sift	Benign	0.28	T
Sift4G	Benign	0.12	T
Polyphen		0.0030	B
Vest4		0.089
MutPred		0.16		Loss of methylation at K654 (P = 0.0028)
MVP		0.014
ClinPred		0.065	T
GERP RS		2.7
Varity_R		0.070
gMVP		0.0062
Mutation Taster		=96/4	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: rs371103290; hg19: chr5-109756295;