NM_001039763.4:c.1787T>C

Variant names:

• chr5-110424833-A-G
• rs191599718
• NM_001039763.4:c.1787T>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001039763.4(TMEM232):​c.1787T>C​(p.Ile596Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00153 in 1,548,804 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (5 hom.)
• Consequence: TMEM232 NM_001039763.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.75
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.037774056).
• BS2: High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM232	NM_001039763.4	c.1787T>C	p.Ile596Thr	missense_variant	Exon 13 of 14	ENST00000455884.7	NP_001034852.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM232	ENST00000455884.7	c.1787T>C	p.Ile596Thr	missense_variant	Exon 13 of 14	2	NM_001039763.4	ENSP00000401477.2

Frequencies

GnomAD3 genomes AF: 0.00104 AC: 158 AN: 152154 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00199

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000949 AC: 144 AN: 151760 AF XY: 0.000932

Gnomad AFR exome AF: 0.000255

Gnomad AMR exome AF: 0.000124

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000591

Gnomad NFE exome AF: 0.00209

Gnomad OTH exome AF: 0.000701

GnomAD4 exome AF: 0.00159 AC: 2214 AN: 1396532 Hom.: 5 Cov.: 30 AF XY: 0.00159 AC XY: 1094 AN XY: 688742

African (AFR) AF: 0.000127 AC: 4 AN: 31476

American (AMR) AF: 0.0000847 AC: 3 AN: 35418

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25084

East Asian (EAS) AF: 0.00 AC: 0 AN: 35586

South Asian (SAS) AF: 0.000127 AC: 10 AN: 78656

European-Finnish (FIN) AF: 0.000772 AC: 38 AN: 49234

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5686

European-Non Finnish (NFE) AF: 0.00195 AC: 2098 AN: 1077496

Other (OTH) AF: 0.00105 AC: 61 AN: 57896

GnomAD4 genome AF: 0.00104 AC: 158 AN: 152272 Hom.: 0 Cov.: 32 AF XY: 0.000994 AC XY: 74 AN XY: 74464

African (AFR) AF: 0.000289 AC: 12 AN: 41568

American (AMR) AF: 0.000131 AC: 2 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.000565 AC: 6 AN: 10622

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

European-Non Finnish (NFE) AF: 0.00199 AC: 135 AN: 67984

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00158 Hom.: 0

Bravo AF: 0.000918

TwinsUK AF: 0.00297 AC: 11

ALSPAC AF: 0.00156 AC: 6

ESP6500AA AF: 0.00145 AC: 2

ESP6500EA AF: 0.00283 AC: 9

ExAC AF: 0.000833 AC: 18

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 10, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1787T>C (p.I596T) alteration is located in exon 13 (coding exon 12) of the TMEM232 gene. This alteration results from a T to C substitution at nucleotide position 1787, causing the isoleucine (I) at amino acid position 596 to be replaced by a threonine (T). 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	0.17
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.81	L
PhyloP100		4.8
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.094
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.73	P
Vest4		0.66
MVP		0.067
ClinPred		0.050	T
GERP RS		4.7
Varity_R		0.17
gMVP		0.057
Mutation Taster		=90/10	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: rs191599718; hg19: chr5-109760534;