chr22-38221702-C-A

Position:

• chr22-38221702-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_012264.5(TMEM184B):​c.991G>T​(p.Ala331Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEM184B NM_012264.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.88

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37830982).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM184B	NM_012264.5	c.991G>T	p.Ala331Ser	missense_variant	9/9	ENST00000361906.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM184B	ENST00000361906.8	c.991G>T	p.Ala331Ser	missense_variant	9/9	1	NM_012264.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

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

Jun 05, 2023

The c.991G>T (p.A331S) alteration is located in exon 9 (coding exon 8) of the TMEM184B gene. This alteration results from a G to T substitution at nucleotide position 991, causing the alanine (A) at amino acid position 331 to be replaced by a serine (S). 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	0.11
BayesDel_addAF	Uncertain	0.089	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.035	T;T
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	.;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.38	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.2	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.14
Sift	Benign	0.24	T;T
Sift4G	Benign	0.40	T;T
Polyphen		0.085	B;B
Vest4		0.62
MutPred		0.43		Gain of disorder (P = 0.0211);Gain of disorder (P = 0.0211);
MVP		0.23
MPC		0.50
ClinPred		0.84	D
GERP RS		5.3
Varity_R		0.11
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr22-38617709; COSMIC: COSV62672458; COSMIC: COSV62672458;