5-83065056-G-C

Position:

• chr5-83065056-G-C

Variant summary

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

The NM_174909.5(TMEM167A):​c.65C>G​(p.Ala22Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: TMEM167A NM_174909.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.60

Genes affected

TMEM167A (HGNC:28330): (transmembrane protein 167A) Involved in constitutive secretory pathway. Located in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

TMEM167A (HGNC:):

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
TMEM167A	NM_174909.5	c.65C>G	p.Ala22Gly	missense_variant	2/4	ENST00000502346.2	NP_777569.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM167A	ENST00000502346.2	c.65C>G	p.Ala22Gly	missense_variant	2/4	1	NM_174909.5	ENSP00000424707.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

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

Jan 03, 2024

The c.65C>G (p.A22G) alteration is located in exon 2 (coding exon 2) of the TMEM167A gene. This alteration results from a C to G substitution at nucleotide position 65, causing the alanine (A) at amino acid position 22 to be replaced by a glycine (G). 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	0.69
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.42	T
Eigen	Uncertain	0.56
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.47	T
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.53
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.53	P
Vest4		0.62
MutPred		0.58		Loss of stability (P = 0.1452);
MVP		0.20
MPC		0.55
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.45
gMVP		0.88

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: chr5-82360875;