1-203007774-T-A

Position:

• chr1-203007774-T-A

Variant summary

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

The NM_138391.6(TMEM183A):​c.110T>A​(p.Val37Glu) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEM183A NM_138391.6 missense, splice_region
• Scores: Splicing: ADA: 0.2589
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.37

Genes affected

TMEM183A (HGNC:20173): (transmembrane protein 183A) Predicted to be involved in regulation of protein stability. Predicted to be integral component of membrane. Predicted to be part of SCF ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM183A	NM_138391.6	c.110T>A	p.Val37Glu	missense_variant, splice_region_variant	2/8	ENST00000367242.4	NP_612400.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM183A	ENST00000367242.4	c.110T>A	p.Val37Glu	missense_variant, splice_region_variant	2/8	1	NM_138391.6	ENSP00000356211.3
TMEM183A	ENST00000468449.5	n.1T>A		non_coding_transcript_exon_variant	1/5	3
TMEM183A	ENST00000543891.5	n.372T>A		non_coding_transcript_exon_variant	1/4	3

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

May 07, 2024

The c.110T>A (p.V37E) alteration is located in exon 2 (coding exon 2) of the TMEM183A gene. This alteration results from a T to A substitution at nucleotide position 110, causing the valine (V) at amino acid position 37 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	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	27
DANN	Uncertain	0.98
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.89	D
M_CAP	Uncertain	0.22	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.37
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.50	P
Vest4		0.91
MutPred		0.38		Loss of sheet (P = 7e-04);
MVP		0.28
MPC		1.3
ClinPred		0.98	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.79
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.26
dbscSNV1_RF	Benign	0.65
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: chr1-202976902;