chr12-71698975-T-A

Position:

• chr12-71698975-T-A

Variant summary

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

The ENST00000266673.10(TMEM19):​c.713T>A​(p.Phe238Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM19 ENST00000266673.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.09

Genes affected

TMEM19 (HGNC:25605): (transmembrane protein 19) Predicted to be integral component of membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000258064 (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=0.1723668).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM19	NM_018279.4	c.713T>A	p.Phe238Tyr	missense_variant	5/6	ENST00000266673.10	NP_060749.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM19	ENST00000266673.10	c.713T>A	p.Phe238Tyr	missense_variant	5/6	1	NM_018279.4	ENSP00000266673.5
ENSG00000258064	ENST00000548802.1	n.*523T>A		downstream_gene_variant		3		ENSP00000454911.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251492 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135920

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

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

Jun 05, 2024

The c.713T>A (p.F238Y) alteration is located in exon 5 (coding exon 5) of the TMEM19 gene. This alteration results from a T to A substitution at nucleotide position 713, causing the phenylalanine (F) at amino acid position 238 to be replaced by a tyrosine (Y). 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	0.15
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	19
DANN	Benign	0.90
DEOGEN2	Benign	0.0047	T;.;.;.
Eigen	Benign	-0.029
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.72	T;T;T;T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.17	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.83	L;L;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	0.86	N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.92	T;T;T;T
Sift4G	Benign	0.81	T;T;T;T
Polyphen		0.0050	B;B;.;.
Vest4		0.47
MutPred		0.65		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);.;.;
MVP		0.076
MPC		0.30
ClinPred		0.34	T
GERP RS		6.2
Varity_R		0.091
gMVP		0.80

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

LitVar

Other links and lift over

dbSNP: rs1306166351; hg19: chr12-72092755;