rs144429031

Variant names:

• chr5-110420724-T-A
• rs144429031
• NM_001039763.4:c.1830A>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001039763.4(TMEM232):​c.1830A>T​(p.Glu610Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000137 in 1,525,222 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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. E610G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00080 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000063 (1 hom.)
• Consequence: TMEM232 NM_001039763.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.59
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0063450634).

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.1830A>T	p.Glu610Asp	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.1830A>T	p.Glu610Asp	missense	Exon 14 of 14	ENSP00000401477.2	C9JQI7-1
	TMEM232	ENST00000512003.7	TSL:1	n.*1124A>T		non_coding_transcript_exon	Exon 11 of 11	ENSP00000427785.2	E5RG73
	TMEM232	ENST00000515518.6	TSL:1	n.1502A>T		non_coding_transcript_exon	Exon 12 of 13

Frequencies

GnomAD3 genomes AF: 0.000782 AC: 119 AN: 152160 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00282

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000112 AC: 14 AN: 124794 AF XY: 0.000132

Gnomad AFR exome AF: 0.00227

Gnomad AMR exome AF: 0.0000474

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000634 AC: 87 AN: 1372944 Hom.: 1 Cov.: 30 AF XY: 0.0000532 AC XY: 36 AN XY: 677112

African (AFR) AF: 0.00235 AC: 72 AN: 30610

American (AMR) AF: 0.0000603 AC: 2 AN: 33172

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25024

East Asian (EAS) AF: 0.00 AC: 0 AN: 35206

South Asian (SAS) AF: 0.00 AC: 0 AN: 76074

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33814

Middle Eastern (MID) AF: 0.000529 AC: 3 AN: 5672

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1075866

Other (OTH) AF: 0.000174 AC: 10 AN: 57506

GnomAD4 genome AF: 0.000801 AC: 122 AN: 152278 Hom.: 0 Cov.: 32 AF XY: 0.000806 AC XY: 60 AN XY: 74472

African (AFR) AF: 0.00289 AC: 120 AN: 41584

American (AMR) AF: 0.0000654 AC: 1 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67984

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000434 Hom.: 0

Bravo AF: 0.000880

ExAC AF: 0.0000667 AC: 1

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	0.24
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	11
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0049	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.0063	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.6
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.046
Sift	Benign	0.035	D
Sift4G	Benign	0.22	T
Polyphen		0.73	P
Vest4		0.12
MutPred		0.11		Loss of helix (P = 0.0444)
MVP		0.040
ClinPred		0.028	T
GERP RS		4.7
Varity_R		0.12
gMVP		0.029
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs144429031; hg19: chr5-109756425;