Genetic Variant TM4SF19:p.Pro252Pro (chr3-196320042-A-C) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The ENST00000446879.5(TM4SF19):c.756T>G(p.Pro252Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000126 in 397,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

TM4SF19
ENST00000446879.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

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.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

BP6

Variant 3-196320042-A-C is Benign according to our data. Variant chr3-196320042-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2654509.Status of the report is criteria_provided_single_submitter, 1 stars.

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>G	intron	N/A
TM4SF19-AS1	NR_046724.1	n.106+1605A>C	intron	N/A
TM4SF19-AS1	NR_121665.1	n.106+1605A>C	intron	N/A

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes

AF:

0.00000681

AC:

AN:

146856

Hom.:

Cov.:

show subpopulations

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:

0.0000150

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000133

AC:

AN:

74964

AF XY:

0.0000247

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:

0.0000353

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000160

AC:

AN:

250172

Hom.:

Cov.:

AF XY:

0.0000278

AC XY:

AN XY:

143948

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

5814

American (AMR)

AF:

0.00

AC:

AN:

16672

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:

0.0000286

AC:

AN:

139998

Other (OTH)

AF:

0.00

AC:

AN:

11748

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.563

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000681

AC:

AN:

146856

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

71362

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39598

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:

9896

Middle Eastern (MID)

AF:

0.00

AC:

AN:

302

European-Non Finnish (NFE)

AF:

0.0000150

AC:

AN:

66886

Other (OTH)

AF:

0.00

AC:

AN:

2010

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000169

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

5.5

(source)

DANN

Benign

0.54

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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