chr12-129073928-C-T

Position:

• chr12-129073928-C-T

Variant summary

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

The NM_133448.3(TMEM132D):​c.3247G>A​(p.Gly1083Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000208 in 1,438,998 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TMEM132D NM_133448.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.83

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=0.19196922).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM132D	NM_133448.3	c.3247G>A	p.Gly1083Arg	missense_variant	9/9	ENST00000422113.7
LOC124903086	XR_007063612.1	n.86+87C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM132D	ENST00000422113.7	c.3247G>A	p.Gly1083Arg	missense_variant	9/9	1	NM_133448.3	P1
TMEM132D	ENST00000389441.8	c.1861G>A	p.Gly621Arg	missense_variant	4/4	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000208 AC: 3 AN: 1438998 Hom.: 0 Cov.: 29 AF XY: 0.00000140 AC XY: 1 AN XY: 713668

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000272

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

research

HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology

Apr 16, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	.;T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.21
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.1	.;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.28	T
PROVEAN	Pathogenic	-5.9	D;D
REVEL	Benign	0.12
Sift	Benign	0.050	D;D
Sift4G	Benign	0.075	T;T
Polyphen		0.85	P;B
Vest4		0.19
MutPred		0.42		.;Gain of solvent accessibility (P = 0.0037);
MVP		0.23
MPC		0.65
ClinPred		0.94	D
GERP RS		3.5
Varity_R		0.28
gMVP		0.12

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

LitVar

Other links and lift over

dbSNP: rs1593250509; hg19: chr12-129558473;