19-42313476-G-A

Position:

• chr19-42313476-G-A

Variant summary

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

The NM_173633.3(TMEM145):​c.100G>A​(p.Gly34Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000842 in 1,188,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 8.4e-7 (0 hom.)
• Consequence: TMEM145 NM_173633.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.685

Genes affected

TMEM145 (HGNC:26912): (transmembrane protein 145) Predicted to be involved in G protein-coupled receptor signaling pathway and response to pheromone. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM145 (HGNC:):

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=0.42238602).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM145	NM_173633.3	c.100G>A	p.Gly34Ser	missense_variant	1/15	ENST00000301204.8	NP_775904.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM145	ENST00000301204.8	c.100G>A	p.Gly34Ser	missense_variant	1/15	2	NM_173633.3	ENSP00000301204.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 8.42e-7 AC: 1 AN: 1188006 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 577074

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000210

GnomAD4 genome Cov.: 31

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 01, 2023

The c.100G>A (p.G34S) alteration is located in exon 1 (coding exon 1) of the TMEM145 gene. This alteration results from a G to A substitution at nucleotide position 100, causing the glycine (G) at amino acid position 34 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	Pathogenic	0.91
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.84	T;T
M_CAP	Pathogenic	0.77	D
MetaRNN	Benign	0.42	T;T
MetaSVM	Benign	-0.36	T
MutationAssessor	Uncertain	2.4	M;.
MutationTaster	Benign	0.94	D
PrimateAI	Pathogenic	0.89	D
PROVEAN	Uncertain	-3.1	D;.
REVEL	Uncertain	0.41
Sift	Pathogenic	0.0	D;.
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.17
MutPred		0.54		Gain of relative solvent accessibility (P = 0.0082);Gain of relative solvent accessibility (P = 0.0082);
MVP		0.50
MPC		1.1
ClinPred		0.99	D
GERP RS		2.3
Varity_R		0.61
gMVP		0.69

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: chr19-42817628;