17-43215897-T-A

Position:

• chr17-43215897-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145041.4(TMEM106A):​c.385T>A​(p.Ser129Thr) variant causes a missense change involving the alteration of a non-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: 32)
• Consequence: TMEM106A NM_145041.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.28

Genes affected

TMEM106A (HGNC:28288): (transmembrane protein 106A) Predicted to be involved in several processes, including glycoprotein biosynthetic process; positive regulation of cytokine production; and positive regulation of intracellular signal transduction. Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM106A (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.240964).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM106A	NM_145041.4	c.385T>A	p.Ser129Thr	missense_variant	5/9	ENST00000612339.4	NP_659478.1
TMEM106A	NM_001291586.2	c.385T>A	p.Ser129Thr	missense_variant	5/9		NP_001278515.1
TMEM106A	NM_001291588.2	c.385T>A	p.Ser129Thr	missense_variant	4/7		NP_001278517.1
TMEM106A	NM_001291587.2	c.241T>A	p.Ser81Thr	missense_variant	6/10		NP_001278516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM106A	ENST00000612339.4	c.385T>A	p.Ser129Thr	missense_variant	5/9	2	NM_145041.4	ENSP00000483246.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Feb 05, 2024

The c.385T>A (p.S129T) alteration is located in exon 5 (coding exon 3) of the TMEM106A gene. This alteration results from a T to A substitution at nucleotide position 385, causing the serine (S) at amino acid position 129 to be replaced by a threonine (T). 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	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	T;T;.;T;T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.79	T;.;T;T;T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.24	T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.5	.;M;.;.;M
MutationTaster	Benign	0.79	D;D;D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.38	.;.;N;N;.
REVEL	Benign	0.15
Sift	Benign	0.81	.;.;T;T;.
Sift4G	Benign	0.39	T;T;T;T;T
Polyphen		1.0	.;D;.;D;D
Vest4		0.41, 0.39, 0.45
MutPred		0.56		Gain of catalytic residue at S129 (P = 0.0461);Gain of catalytic residue at S129 (P = 0.0461);.;Gain of catalytic residue at S129 (P = 0.0461);Gain of catalytic residue at S129 (P = 0.0461);
MVP		0.13
ClinPred		0.92	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.090
gMVP		0.11

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-41367916;