12-129074060-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_133448.3(TMEM132D):c.3115A>G(p.Thr1039Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM132D NM_133448.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.88

Genes affected

TMEM132D (HGNC:29411): (transmembrane protein 132D)

LOC124903086 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1081855).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM132D	NM_133448.3	c.3115A>G	p.Thr1039Ala	missense_variant	9/9	ENST00000422113.7
LOC124903086	XR_007063612.1	n.86+219T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM132D	ENST00000422113.7	c.3115A>G	p.Thr1039Ala	missense_variant	9/9	1	NM_133448.3	P1
TMEM132D	ENST00000389441.8	c.1729A>G	p.Thr577Ala	missense_variant	4/4	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 06, 2023

The c.3115A>G (p.T1039A) alteration is located in exon 9 (coding exon 9) of the TMEM132D gene. This alteration results from a A to G substitution at nucleotide position 3115, causing the threonine (T) at amino acid position 1039 to be replaced by an alanine (A). 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	0.19
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	20
Dann	Uncertain	0.98
Eigen	Benign	-0.033
Eigen_PC	Benign	-0.054
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.79	D;D
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-2.2	N;D
REVEL	Benign	0.11
Sift	Benign	0.18	T;T
Sift4G	Uncertain	0.054	T;T
Polyphen		0.81	P;B
Vest4		0.17
MutPred		0.26		.;Gain of catalytic residue at P1034 (P = 5e-04);
MVP		0.16
MPC		0.30
ClinPred		0.82	D
GERP RS		1.8
Varity_R		0.13
gMVP		0.44

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-129558605;