1-203007470-C-T

Variant names:

• chr1-203007470-C-T
• rs369780991
• NM_138391.6:c.5C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_138391.6(TMEM183A):​c.5C>T​(p.Ala2Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000023 in 1,302,970 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A2P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: TMEM183A NM_138391.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.79
• Publications: 0 publications found

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]

MGAT4FP (HGNC:49419): (MGAT4 family member F, pseudogene)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32492578).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138391.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM183A	NM_138391.6	MANE Select	c.5C>T	p.Ala2Val	missense	Exon 1 of 8	NP_612400.3
	TMEM183A	NM_001322956.2		c.5C>T	p.Ala2Val	missense	Exon 1 of 8	NP_001309885.1
	TMEM183A	NM_001322958.2		c.5C>T	p.Ala2Val	missense	Exon 1 of 7	NP_001309887.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM183A	ENST00000367242.4	TSL:1 MANE Select	c.5C>T	p.Ala2Val	missense	Exon 1 of 8	ENSP00000356211.3	Q8IXX5-1
	TMEM183A	ENST00000881146.1		c.5C>T	p.Ala2Val	missense	Exon 1 of 9	ENSP00000551205.1
	TMEM183A	ENST00000965091.1		c.5C>T	p.Ala2Val	missense	Exon 1 of 8	ENSP00000635150.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000230 AC: 3 AN: 1302970 Hom.: 0 Cov.: 31 AF XY: 0.00000157 AC XY: 1 AN XY: 637314

African (AFR) AF: 0.00 AC: 0 AN: 26712

American (AMR) AF: 0.00 AC: 0 AN: 28318

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22094

East Asian (EAS) AF: 0.00 AC: 0 AN: 30760

South Asian (SAS) AF: 0.00 AC: 0 AN: 72658

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32650

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3758

European-Non Finnish (NFE) AF: 9.69e-7 AC: 1 AN: 1032302

Other (OTH) AF: 0.0000372 AC: 2 AN: 53718

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0051	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.8
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.073
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.84	P
Vest4		0.50
MutPred		0.31		Gain of MoRF binding (P = 0.0911)
MVP		0.043
MPC		0.57
ClinPred		0.98	D
GERP RS		4.8
PromoterAI		-0.022	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.53
gMVP		0.45
Mutation Taster		=78/22	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

dbSNP: rs369780991; hg19: chr1-202976598;