rs115896544

Variant names:

• chr3-100732499-T-C
• rs115896544
• NM_006070.6:c.416-9T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-100732499-T-C
• chr3-100732499-T-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006070.6(TFG):​c.416-9T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0029 in 1,595,378 control chromosomes in the GnomAD database, including 116 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (57 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (59 hom.)
• Consequence: TFG NM_006070.6 intron
• Scores: Splicing: ADA: 0.0001047
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.485
• Publications: 1 publications found

Genes affected

TFG (HGNC:11758): (trafficking from ER to golgi regulator) There are several documented fusion oncoproteins encoded partially by this gene. This gene also participates in several oncogenic rearrangements resulting in anaplastic lymphoma and mixoid chondrosarcoma, and may play a role in the NF-kappaB pathway. Multiple transcript variants have been found for this gene. [provided by RefSeq, Sep 2010]

TFG Gene-Disease associations (from GenCC):

• hereditary motor and sensory neuropathy, Okinawa type

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia
• hereditary spastic paraplegia 57

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia
• autosomal dominant Charcot-Marie-Tooth disease type 2 due to TFG mutation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 3-100732499-T-C is Benign according to our data. Variant chr3-100732499-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 378719.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0536 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006070.6. 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
	TFG	NM_006070.6	MANE Select	c.416-9T>C		intron	N/A	NP_006061.2
	TFG	NM_001007565.2		c.416-9T>C		intron	N/A	NP_001007566.1	Q92734-1
	TFG	NM_001195478.2		c.416-9T>C		intron	N/A	NP_001182407.1	Q92734-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFG	ENST00000240851.9	TSL:1 MANE Select	c.416-9T>C		intron	N/A	ENSP00000240851.4	Q92734-1
	TFG	ENST00000476228.5	TSL:1	c.416-9T>C		intron	N/A	ENSP00000417952.1	Q92734-2
	TFG	ENST00000615993.2	TSL:1	c.416-9T>C		intron	N/A	ENSP00000479269.2	Q92734-4

Frequencies

GnomAD3 genomes AF: 0.0156 AC: 2382 AN: 152206 Hom.: 55 Cov.: 32

Gnomad AFR AF: 0.0553

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00360

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00813

GnomAD2 exomes AF: 0.00403 AC: 940 AN: 233520 AF XY: 0.00283

Gnomad AFR exome AF: 0.0545

Gnomad AMR exome AF: 0.00212

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000368

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.00155 AC: 2240 AN: 1443054 Hom.: 59 Cov.: 30 AF XY: 0.00133 AC XY: 953 AN XY: 717804

African (AFR) AF: 0.0570 AC: 1823 AN: 31986

American (AMR) AF: 0.00243 AC: 96 AN: 39436

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25162

East Asian (EAS) AF: 0.00 AC: 0 AN: 39460

South Asian (SAS) AF: 0.000169 AC: 14 AN: 82686

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53082

Middle Eastern (MID) AF: 0.00408 AC: 22 AN: 5392

European-Non Finnish (NFE) AF: 0.0000678 AC: 75 AN: 1106396

Other (OTH) AF: 0.00353 AC: 210 AN: 59454

GnomAD4 genome AF: 0.0157 AC: 2392 AN: 152324 Hom.: 57 Cov.: 32 AF XY: 0.0152 AC XY: 1130 AN XY: 74482

African (AFR) AF: 0.0554 AC: 2304 AN: 41560

American (AMR) AF: 0.00353 AC: 54 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68032

Other (OTH) AF: 0.00804 AC: 17 AN: 2114

Alfa AF: 0.00570 Hom.: 13

Bravo AF: 0.0178

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Hereditary motor and sensory neuropathy, Okinawa type;C3714897:Hereditary spastic paraplegia 57 (2)
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	TFG-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.2
DANN	Benign	0.79
PhyloP100		0.48
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00010
dbscSNV1_RF	Benign	0.0040
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: rs115896544; hg19: chr3-100451343;