chr7-138803010-C-T

Position:

• chr7-138803010-C-T

Variant summary

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

The NM_001085429.2(TMEM213):​c.265C>T​(p.Leu89Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEM213 NM_001085429.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.57

Genes affected

TMEM213 (HGNC:27220): (transmembrane protein 213) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.20915303).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM213	NM_001085429.2	c.265C>T	p.Leu89Phe	missense_variant	3/3	ENST00000442682.7	NP_001078898.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM213	ENST00000442682.7	c.265C>T	p.Leu89Phe	missense_variant	3/3	1	NM_001085429.2	ENSP00000390407.2
TMEM213	ENST00000397602.7	c.262C>T	p.Leu88Phe	missense_variant	3/3	1		ENSP00000380727.3
TMEM213	ENST00000458494.1	c.193C>T	p.Leu65Phe	missense_variant	2/2	4		ENSP00000393891.1
TMEM213	ENST00000413208.1	c.154+1612C>T		intron_variant		3		ENSP00000401570.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Aug 05, 2024

The c.265C>T (p.L89F) alteration is located in exon 3 (coding exon 3) of the TMEM213 gene. This alteration results from a C to T substitution at nucleotide position 265, causing the leucine (L) at amino acid position 89 to be replaced by a phenylalanine (F). 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	0.14
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	.;T;.
Eigen	Benign	0.12
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.86	D;D;D
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.2	.;M;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-2.7	D;D;D
REVEL	Benign	0.063
Sift	Benign	0.15	T;T;T
Sift4G	Benign	0.29	T;T;T
Polyphen		0.71	P;P;.
Vest4		0.29
MutPred		0.24		.;Gain of methylation at K93 (P = 0.1085);.;
MVP		0.072
MPC		0.82
ClinPred		0.95	D
GERP RS		3.9
Varity_R		0.17
gMVP		0.33

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: chr7-138487755;