rs369780991

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-203007470-C-G
• chr1-203007470-C-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_138391.6(TMEM183A):​c.5C>G​(p.Ala2Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000741 in 1,455,326 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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: 𝑓 0.00031 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00079 (3 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09185141).
• BS2: High Homozygotes in GnomAdExome4 at 3 gene

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>G	p.Ala2Gly	missense	Exon 1 of 8	NP_612400.3
	TMEM183A	NM_001322956.2		c.5C>G	p.Ala2Gly	missense	Exon 1 of 8	NP_001309885.1
	TMEM183A	NM_001322958.2		c.5C>G	p.Ala2Gly	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>G	p.Ala2Gly	missense	Exon 1 of 8	ENSP00000356211.3	Q8IXX5-1
	TMEM183A	ENST00000881146.1		c.5C>G	p.Ala2Gly	missense	Exon 1 of 9	ENSP00000551205.1
	TMEM183A	ENST00000965091.1		c.5C>G	p.Ala2Gly	missense	Exon 1 of 8	ENSP00000635150.1

Frequencies

GnomAD3 genomes AF: 0.000309 AC: 47 AN: 152240 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000146 AC: 13 AN: 89206 AF XY: 0.000217

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000358

Gnomad OTH exome AF: 0.000365

GnomAD4 exome AF: 0.000792 AC: 1032 AN: 1302968 Hom.: 3 Cov.: 31 AF XY: 0.000736 AC XY: 469 AN XY: 637314

African (AFR) AF: 0.000112 AC: 3 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: 0.000978 AC: 1010 AN: 1032300

Other (OTH) AF: 0.000354 AC: 19 AN: 53718

GnomAD4 genome AF: 0.000308 AC: 47 AN: 152358 Hom.: 0 Cov.: 33 AF XY: 0.000282 AC XY: 21 AN XY: 74502

African (AFR) AF: 0.000240 AC: 10 AN: 41590

American (AMR) AF: 0.00 AC: 0 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000544 AC: 37 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000276 Hom.: 0

Bravo AF: 0.000268

ExAC AF: 0.0000586 AC: 5

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	Benign	0.12
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0039	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		2.8
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.048
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.69	P
Vest4		0.24
MVP		0.068
MPC		0.57
ClinPred		0.27	T
GERP RS		4.8
PromoterAI		-0.013	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.45
gMVP		0.34
Mutation Taster		=74/26	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;