Variant 3-196327503-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_138461.4(TM4SF19):c.88G>C(p.Ala30Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00281 in 1,614,134 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.0026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 11 hom. )

Consequence

TM4SF19
NM_138461.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.842

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014147311).

BS2

High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TM4SF19	NM_138461.4 linkuse as main transcript	c.88G>C	p.Ala30Pro	missense_variant	2/5	ENST00000273695.4	NP_612470.2
TM4SF19-DYNLT2B	NR_037950.1 linkuse as main transcript	n.246G>C		non_coding_transcript_exon_variant	2/6
TM4SF19	NM_001204897.2 linkuse as main transcript	c.88G>C	p.Ala30Pro	missense_variant	2/5		NP_001191826.1
TM4SF19	NM_001204898.2 linkuse as main transcript	c.88G>C	p.Ala30Pro	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.88G>C	p.Ala30Pro	missense_variant	2/5	1	NM_138461.4	ENSP00000273695	P1	Q96DZ7-1
TM4SF19	ENST00000446879.5 linkuse as main transcript	c.88G>C	p.Ala30Pro	missense_variant	2/6	1		ENSP00000395280
TM4SF19	ENST00000454715.5 linkuse as main transcript	c.88G>C	p.Ala30Pro	missense_variant	2/4	1		ENSP00000387728		Q96DZ7-2

Frequencies

GnomAD3 genomes

AF:

0.00265

AC:

403

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00687

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00414

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00250

AC:

628

AN:

251278

Hom.:

AF XY:

0.00261

AC XY:

354

AN XY:

135834

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000694

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00144

Gnomad FIN exome

AF:

0.00568

Gnomad NFE exome

AF:

0.00368

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00283

AC:

4131

AN:

1461804

Hom.:

Cov.:

AF XY:

0.00286

AC XY:

2083

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000872

Gnomad4 ASJ exome

AF:

0.000230

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00131

Gnomad4 FIN exome

AF:

0.00531

Gnomad4 NFE exome

AF:

0.00313

Gnomad4 OTH exome

AF:

0.00262

GnomAD4 genome

AF:

0.00265

AC:

403

AN:

152330

Hom.:

Cov.:

AF XY:

0.00260

AC XY:

194

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00687

Gnomad4 NFE

AF:

0.00414

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00302

Hom.:

Bravo

AF:

0.00188

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00493

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00267

AC:

ExAC

AF:

0.00274

AC:

332

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Nov 06, 2015

- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.72

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0085

.;.;T

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.76

T;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.014

T;T;T

MetaSVM

Benign

-0.68

MutationAssessor

Uncertain

2.4

.;M;M

MutationTaster

Benign

0.88

D;D;D

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.0

N;N;N

REVEL

Benign

0.23

Sift

Uncertain

0.0020

D;T;T

Sift4G

Pathogenic

0.0010

D;T;T

Polyphen

1.0

D;.;D

Vest4

0.68

MVP

0.44

MPC

1.2

ClinPred

0.023

GERP RS

4.9

Varity_R

0.81

gMVP

0.84

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over