rs773531524

Variant names:

• chr22-38231330-C-G
• rs773531524
• NM_012264.5:c.363G>C

Your query was ambiguous. Multiple possible variants found:

• chr22-38231330-C-G
• chr22-38231330-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012264.5(TMEM184B):​c.363G>C​(p.Leu121Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,613,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: TMEM184B NM_012264.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.21
• Publications: 0 publications found

Genes affected

TMEM184B (HGNC:1310): (transmembrane protein 184B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM184B-AS1 (HGNC:56716): (TMEM184B antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.079508275).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012264.5. 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
	TMEM184B	NM_012264.5	MANE Select	c.363G>C	p.Leu121Phe	missense	Exon 4 of 9	NP_036396.2	Q9Y519
	TMEM184B	NM_001195071.1		c.363G>C	p.Leu121Phe	missense	Exon 4 of 9	NP_001182000.1	Q9Y519
	TMEM184B	NM_001195072.2		c.165G>C	p.Leu55Phe	missense	Exon 5 of 10	NP_001182001.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM184B	ENST00000361906.8	TSL:1 MANE Select	c.363G>C	p.Leu121Phe	missense	Exon 4 of 9	ENSP00000355210.3	Q9Y519
	TMEM184B	ENST00000361684.8	TSL:1	c.363G>C	p.Leu121Phe	missense	Exon 4 of 9	ENSP00000354441.4	Q9Y519
	TMEM184B	ENST00000436674.5	TSL:1	n.*245G>C		non_coding_transcript_exon	Exon 5 of 10	ENSP00000413085.1	F2Z397

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152122 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000795 AC: 2 AN: 251486 AF XY: 0.0000147

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: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000164 AC: 24 AN: 1461712 Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12 AN XY: 727172

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000189 AC: 21 AN: 1111840

Other (OTH) AF: 0.0000166 AC: 1 AN: 60392

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152122 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74314

African (AFR) AF: 0.00 AC: 0 AN: 41390

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.00000824 AC: 1

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	0.044
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Benign	0.84
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.51
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-2.7	N
PhyloP100		2.2
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	5.2	N
REVEL	Benign	0.13
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.28
MutPred		0.52		Loss of stability (P = 0.1242)
MVP		0.043
MPC		0.58
ClinPred		0.076	T
GERP RS		2.9
Varity_R		0.042
gMVP		0.38
Mutation Taster		=64/36	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: rs773531524; hg19: chr22-38627336;