Variant 3-196327577-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138461.4(TM4SF19):c.14C>A(p.Pro5His) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

TM4SF19
NM_138461.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.797

Variant links:

Genes affected

TM4SF19 (HGNC:25167): (transmembrane 4 L six family member 19) The protein encoded by this gene is a member of the four-transmembrane L6 superfamily. Members of this family function in various cellular processes including cell proliferation, motility, and adhesion via their interactions with integrins. In human brain tissue, this gene is expressed at high levels in the parietal lobe, occipital lobe, hippocampus, pons, white matter, corpus callosum, and cerebellum. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2017]

TM4SF19 links:

TM4SF19-DYNLT2B (HGNC:):

TM4SF19-DYNLT2B links:

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ACMG classification

Classification made for transcript

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=0.16851988).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TM4SF19	NM_138461.4 linkuse as main transcript	c.14C>A	p.Pro5His	missense_variant	2/5	ENST00000273695.4	NP_612470.2
TM4SF19-DYNLT2B	NR_037950.1 linkuse as main transcript	n.172C>A		non_coding_transcript_exon_variant	2/6
TM4SF19	NM_001204897.2 linkuse as main transcript	c.14C>A	p.Pro5His	missense_variant	2/5		NP_001191826.1
TM4SF19	NM_001204898.2 linkuse as main transcript	c.14C>A	p.Pro5His	missense_variant	2/4		NP_001191827.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TM4SF19	ENST00000273695.4 linkuse as main transcript	c.14C>A	p.Pro5His	missense_variant	2/5	1	NM_138461.4	ENSP00000273695	P1	Q96DZ7-1
TM4SF19	ENST00000446879.5 linkuse as main transcript	c.14C>A	p.Pro5His	missense_variant	2/6	1		ENSP00000395280
TM4SF19	ENST00000454715.5 linkuse as main transcript	c.14C>A	p.Pro5His	missense_variant	2/4	1		ENSP00000387728		Q96DZ7-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 28, 2023

The c.14C>A (p.P5H) alteration is located in exon 2 (coding exon 1) of the TM4SF19 gene. This alteration results from a C to A substitution at nucleotide position 14, causing the proline (P) at amino acid position 5 to be replaced by a histidine (H). 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

0.075

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0054

.;.;T

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.36

T;T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.17

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

.;M;M

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.1

N;N;N

REVEL

Benign

0.046

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.015

D;D;D

Polyphen

0.98

D;.;P

Vest4

0.37

MutPred

0.24

Gain of solvent accessibility (P = 0.1045);Gain of solvent accessibility (P = 0.1045);Gain of solvent accessibility (P = 0.1045);

MVP

0.17

MPC

0.77

ClinPred

0.69

GERP RS

2.8

Varity_R

0.069

gMVP

0.24

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over