19-55378073-C-T

Position:

• chr19-55378073-C-T

Variant summary

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

The NM_139172.3(TMEM190):​c.404C>T​(p.Thr135Ile) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: TMEM190 NM_139172.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.397

Genes affected

TMEM190 (HGNC:29632): (transmembrane protein 190) Predicted to enable protein self-association. Predicted to be involved in hematopoietic progenitor cell differentiation. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

(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=0.094119966).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM190	NM_139172.3	c.404C>T	p.Thr135Ile	missense_variant	5/5	ENST00000291934.4	NP_631911.1
TMEM190	XM_017026331.2	c.278C>T	p.Thr93Ile	missense_variant	4/4		XP_016881820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM190	ENST00000291934.4	c.404C>T	p.Thr135Ile	missense_variant	5/5	1	NM_139172.3	ENSP00000291934	P1
	ENST00000595064.1	n.53G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 33

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

Dec 15, 2023

The c.404C>T (p.T135I) alteration is located in exon 5 (coding exon 5) of the TMEM190 gene. This alteration results from a C to T substitution at nucleotide position 404, causing the threonine (T) at amino acid position 135 to be replaced by an isoleucine (I). 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	0.17
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	10
DANN	Benign	0.92
DEOGEN2	Benign	0.19	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.00078	T
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.31	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.049
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.035	D
Polyphen		0.53	P
Vest4		0.12
MutPred		0.14		Loss of glycosylation at T135 (P = 0.0112);
MVP		0.076
MPC		0.52
ClinPred		0.21	T
GERP RS		-1.6
Varity_R		0.15
gMVP		0.044

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: chr19-55889441;