1-205084289-C-T

Variant names:

• chr1-205084289-C-T
• NM_203376.2:c.32G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_203376.2(TMEM81):​c.32G>A​(p.Gly11Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: TMEM81 NM_203376.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.61
• Publications: 0 publications found

Genes affected

TMEM81 (HGNC:32349): (transmembrane protein 81) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM81	NM_203376.2	c.32G>A	p.Gly11Glu	missense_variant	Exon 1 of 1	ENST00000367167.4	NP_976310.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM81	ENST00000367167.4	c.32G>A	p.Gly11Glu	missense_variant	Exon 1 of 1	6	NM_203376.2	ENSP00000356135.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.32G>A (p.G11E) alteration is located in exon 1 (coding exon 1) of the TMEM81 gene. This alteration results from a G to A substitution at nucleotide position 32, causing the glycine (G) at amino acid position 11 to be replaced by a glutamic acid (E). 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	0.25
BayesDel_addAF	Uncertain	0.036	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.6
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.19
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.037	D
Polyphen		0.94	P
Vest4		0.69
MutPred		0.46		Loss of sheet (P = 0.0043);
MVP		0.17
MPC		0.36
ClinPred		0.92	D
GERP RS		2.6
PromoterAI		0.018	Neutral
Varity_R		0.29
gMVP		0.70
Mutation Taster		=100/0	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

hg19: chr1-205053417;