chr3-196320048-T-G

Variant names:

• chr3-196320048-T-G
• rs1187330028
• ENST00000446879.5:c.750A>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The ENST00000446879.5(TM4SF19):​c.750A>C​(p.Arg250Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 381,062 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 0.000015 (0 hom., cov: 28)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: TM4SF19 ENST00000446879.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.445
• Publications: 0 publications found

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

ACMG classification

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=-0.88).
• BP6: Variant 3-196320048-T-G is Benign according to our data. Variant chr3-196320048-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2654510.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.445 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TM4SF19-DYNLT2B	NR_037950.1		n.861+3696A>C		intron	N/A
	TM4SF19-AS1	NR_046724.1		n.106+1611T>G		intron	N/A
	TM4SF19-AS1	NR_121665.1		n.106+1611T>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TM4SF19	ENST00000446879.5	TSL:1	c.750A>C	p.Arg250Arg	synonymous	Exon 6 of 6	ENSP00000395280.1	C9JCD5
	TM4SF19-DYNLT2B	ENST00000442633.1	TSL:1	n.*73+3696A>C		intron	N/A	ENSP00000405973.1
	TM4SF19-AS1	ENST00000420226.2	TSL:2	n.150+1611T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000147 AC: 2 AN: 136122 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000282

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: 0.0000155

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000137 AC: 1 AN: 72750 AF XY: 0.0000252

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: 0.000431

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000817 AC: 2 AN: 244940 Hom.: 0 Cov.: 0 AF XY: 0.0000141 AC XY: 2 AN XY: 141530

African (AFR) AF: 0.00 AC: 0 AN: 5502

American (AMR) AF: 0.00 AC: 0 AN: 16308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7494

East Asian (EAS) AF: 0.00 AC: 0 AN: 7886

South Asian (SAS) AF: 0.00 AC: 0 AN: 48464

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10168

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 822

European-Non Finnish (NFE) AF: 0.0000146 AC: 2 AN: 136888

Other (OTH) AF: 0.00 AC: 0 AN: 11408

GnomAD4 genome AF: 0.0000147 AC: 2 AN: 136122 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 65222

African (AFR) AF: 0.0000282 AC: 1 AN: 35458

American (AMR) AF: 0.00 AC: 0 AN: 12750

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3312

East Asian (EAS) AF: 0.00 AC: 0 AN: 4724

South Asian (SAS) AF: 0.00 AC: 0 AN: 4310

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8112

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.0000155 AC: 1 AN: 64486

Other (OTH) AF: 0.00 AC: 0 AN: 1802

Alfa AF: 0.000169 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.8
DANN	Benign	0.52
PhyloP100		-0.45

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

Other links and lift over

dbSNP: rs1187330028; hg19: chr3-196046919;