Genetic Variant ENST00000446879.5:c.756T>A (chr3-196320042-A-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP7

The ENST00000446879.5(TM4SF19):c.756T>A(p.Pro252Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P252P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TM4SF19
ENST00000446879.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.493

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP7

Synonymous conserved (PhyloP=0.493 with no splicing effect.

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	HGVSc	Effect	Exon Rank
TM4SF19-DYNLT2B	NR_037950.1	n.861+3702T>A	intron	N/A
TM4SF19-AS1	NR_046724.1	n.106+1605A>T	intron	N/A
TM4SF19-AS1	NR_121665.1	n.106+1605A>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TM4SF19	ENST00000446879.5	TSL:1	c.756T>A	p.Pro252Pro	synonymous	Exon 6 of 6	ENSP00000395280.1	C9JCD5
TM4SF19-DYNLT2B	ENST00000442633.1	TSL:1	n.*73+3702T>A		intron	N/A	ENSP00000405973.1
TM4SF19-AS1	ENST00000420226.2	TSL:2	n.150+1605A>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

146858

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

250176

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

143950

African (AFR)

AF:

0.00

AC:

AN:

5814

American (AMR)

AF:

0.00

AC:

AN:

16674

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7514

East Asian (EAS)

AF:

0.00

AC:

AN:

8280

South Asian (SAS)

AF:

0.00

AC:

AN:

48772

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10512

Middle Eastern (MID)

AF:

0.00

AC:

AN:

862

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

140000

Other (OTH)

AF:

0.00

AC:

AN:

11748

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

146858

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

71364

African (AFR)

AF:

0.00

AC:

AN:

39602

American (AMR)

AF:

0.00

AC:

AN:

14450

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3404

East Asian (EAS)

AF:

0.00

AC:

AN:

4872

South Asian (SAS)

AF:

0.00

AC:

AN:

4542

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9894

Middle Eastern (MID)

AF:

0.00

AC:

AN:

302

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66886

Other (OTH)

AF:

0.00

AC:

AN:

2010

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

5.4

(source)

DANN

Benign

0.51

PhyloP100

0.49

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