3-100713570-CATCTA-C

Variant names:

• chr3-100713570-CATCTA-C
• rs202077935
• NM_006070.6:c.-43-70_-43-66delCTAAT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_006070.6(TFG):​c.-43-70_-43-66delCTAAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00912 in 605,210 control chromosomes in the GnomAD database, including 235 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.026 (170 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (65 hom.)
• Consequence: TFG NM_006070.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.23
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 3-100713570-CATCTA-C is Benign according to our data. Variant chr3-100713570-CATCTA-C is described in ClinVar as Benign. ClinVar VariationId is 1301296.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0886 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.-43-70_-43-66delCTAAT		intron	N/A	NP_006061.2
	TFG	NM_001007565.2		c.-43-70_-43-66delCTAAT		intron	N/A	NP_001007566.1	Q92734-1
	TFG	NM_001195478.2		c.-43-70_-43-66delCTAAT		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.-43-72_-43-68delATCTA		intron	N/A	ENSP00000240851.4	Q92734-1
	TFG	ENST00000476228.5	TSL:1	c.-43-72_-43-68delATCTA		intron	N/A	ENSP00000417952.1	Q92734-2
	TFG	ENST00000615993.2	TSL:1	c.-43-72_-43-68delATCTA		intron	N/A	ENSP00000479269.2	Q92734-4

Frequencies

GnomAD3 genomes AF: 0.0262 AC: 3986 AN: 152026 Hom.: 169 Cov.: 32

Gnomad AFR AF: 0.0910

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0110

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: 0.000279

Gnomad OTH AF: 0.0173

GnomAD4 exome AF: 0.00335 AC: 1520 AN: 453066 Hom.: 65 AF XY: 0.00293 AC XY: 677 AN XY: 230882

African (AFR) AF: 0.0991 AC: 1092 AN: 11016

American (AMR) AF: 0.0106 AC: 141 AN: 13288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11068

East Asian (EAS) AF: 0.00 AC: 0 AN: 26152

South Asian (SAS) AF: 0.000213 AC: 3 AN: 14100

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35930

Middle Eastern (MID) AF: 0.00626 AC: 16 AN: 2554

European-Non Finnish (NFE) AF: 0.000158 AC: 50 AN: 315860

Other (OTH) AF: 0.00944 AC: 218 AN: 23098

GnomAD4 genome AF: 0.0263 AC: 3997 AN: 152144 Hom.: 170 Cov.: 32 AF XY: 0.0255 AC XY: 1896 AN XY: 74406

African (AFR) AF: 0.0910 AC: 3774 AN: 41480

American (AMR) AF: 0.0109 AC: 167 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

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

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68012

Other (OTH) AF: 0.0171 AC: 36 AN: 2104

Alfa AF: 0.0241 Hom.: 19

Bravo AF: 0.0321

Asia WGS AF: 0.00433 AC: 16 AN: 3478

ClinVar

ClinVar submissions

Significance: 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
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs202077935; hg19: chr3-100432414;