Genetic Variant ENST00000446879.5:c.634A>G (chr3-196323809-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000446879.5(TM4SF19):c.634A>G(p.Asn212Asp) 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. 15/18 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

TM4SF19
ENST00000446879.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -5.29

Publications

0 publications found

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:49190): (TM4SF19-DYNLT2B readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring transmembrane 4 L six family member 19 (TM4SF19) and Tctex1 domain containing 2 (TCTEX1D2) genes on chromosome 3. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus not expected to produce a protein product. [provided by RefSeq, Mar 2011]

TM4SF19-DYNLT2B links:

TM4SF19-AS1 (HGNC:41085): (TM4SF19 antisense RNA 1)

TM4SF19-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04874316).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000446879.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TM4SF19	NM_138461.4	MANE Select	c.*8A>G		3_prime_UTR	Exon 5 of 5	NP_612470.2	Q96DZ7-1
TM4SF19	NM_001204897.2		c.634A>G	p.Asn212Asp	missense	Exon 5 of 5	NP_001191826.1
TM4SF19	NM_001204898.2		c.*8A>G		3_prime_UTR	Exon 4 of 4	NP_001191827.1	Q96DZ7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TM4SF19	ENST00000446879.5	TSL:1	c.634A>G	p.Asn212Asp	missense	Exon 5 of 6	ENSP00000395280.1	C9JCD5
TM4SF19	ENST00000273695.4	TSL:1 MANE Select	c.*8A>G		3_prime_UTR	Exon 5 of 5	ENSP00000273695.4	Q96DZ7-1
TM4SF19	ENST00000454715.5	TSL:1	c.*8A>G		3_prime_UTR	Exon 4 of 4	ENSP00000387728.1	Q96DZ7-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251448

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.0070

(source)

DANN

Benign

0.70

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.29

M_CAP

Benign

0.0027

MetaRNN

Benign

0.049

MetaSVM

Benign

-1.1

PhyloP100

-5.3

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.67

REVEL

Benign

0.026

Sift

Benign

0.086

Sift4G

Benign

0.23

Polyphen

0.016

Vest4

0.11

MutPred

0.37

Loss of helix (P = 0.028)

MVP

0.055

ClinPred

0.069

GERP RS

-8.7

Mutation Taster

=98/2

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over