chr19-55377620-A-T

Position:

• chr19-55377620-A-T

Variant summary

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

The ENST00000291934.4(TMEM190):​c.122A>T​(p.Glu41Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 152,006 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 30)
• Consequence: TMEM190 ENST00000291934.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.54

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]

ENSG00000269275 (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
TMEM190	NM_139172.3	c.122A>T	p.Glu41Val	missense_variant	3/5	ENST00000291934.4	NP_631911.1
TMEM190	XM_017026331.2	c.95-182A>T		intron_variant			XP_016881820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM190	ENST00000291934.4	c.122A>T	p.Glu41Val	missense_variant	3/5	1	NM_139172.3	ENSP00000291934.3
ENSG00000269275	ENST00000595064.1	n.506T>A		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152006 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152006 Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1 AN XY: 74220

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000113

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 23, 2024

The c.122A>T (p.E41V) alteration is located in exon 3 (coding exon 3) of the TMEM190 gene. This alteration results from a A to T substitution at nucleotide position 122, causing the glutamic acid (E) at amino acid position 41 to be replaced by a valine (V). 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	0.81
BayesDel_addAF	Uncertain	0.082	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T
Eigen	Benign	0.030
Eigen_PC	Benign	-0.044
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.58	T
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.0	L
MutationTaster	Benign	0.50	D
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Benign	0.23
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.96	D
Vest4		0.45
MutPred		0.30		Loss of disorder (P = 0.0531);
MVP		0.37
MPC		1.0
ClinPred		0.96	D
GERP RS		2.2
Varity_R		0.62
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1437416018; hg19: chr19-55888988;