rs11172344

Variant names:

• chr12-57799665-T-C
• rs11172344
• NM_006576.4:c.2346+130A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-57799665-T-C
• chr12-57799665-T-A
• chr12-57799665-T-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006576.4(AVIL):​c.2346+130A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 1,333,376 control chromosomes in the GnomAD database, including 85,676 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.31 (8091 hom., cov: 32)
  • Exomes 𝑓: 0.35 (77585 hom.)
• Consequence: AVIL NM_006576.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.317
• Publications: 24 publications found

Genes affected

AVIL (HGNC:14188): (advillin) The protein encoded by this gene is a member of the gelsolin/villin family of actin regulatory proteins. This protein has structural similarity to villin. It binds actin and may play a role in the development of neuronal cells that form ganglia. [provided by RefSeq, Jul 2008]

TSFM (HGNC:12367): (Ts translation elongation factor, mitochondrial) This gene encodes a mitochondrial translation elongation factor. The encoded protein is an enzyme that catalyzes the exchange of guanine nucleotides on the translation elongation factor Tu during the elongation step of mitchondrial protein translation. Mutations in this gene are associated with combined oxidative phosphorylation deficiency-3 syndrome. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Mar 2010]

TSFM Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
• Leigh syndrome

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 12-57799665-T-C is Benign according to our data. Variant chr12-57799665-T-C is described in ClinVar as Benign. ClinVar VariationId is 1225336.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006576.4. 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
	AVIL	NM_006576.4	MANE Select	c.2346+130A>G		intron	N/A	NP_006567.3
	TSFM	NM_001172697.2		c.572-2890T>C		intron	N/A	NP_001166168.1	P43897-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AVIL	ENST00000549994.2	TSL:4 MANE Select	c.2346+130A>G		intron	N/A	ENSP00000449239.2	O75366-1
	AVIL	ENST00000257861.7	TSL:1	c.2346+130A>G		intron	N/A	ENSP00000257861.3	O75366-1
	TSFM	ENST00000543727.5	TSL:1	c.572-2890T>C		intron	N/A	ENSP00000439342.1	P43897-4

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47389 AN: 151770 Hom.: 8068 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.655

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.266

GnomAD4 exome AF: 0.349 AC: 411987 AN: 1181488 Hom.: 77585 AF XY: 0.354 AC XY: 208278 AN XY: 587854

African (AFR) AF: 0.215 AC: 5759 AN: 26800

American (AMR) AF: 0.337 AC: 10129 AN: 30050

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 5620 AN: 19524

East Asian (EAS) AF: 0.702 AC: 26622 AN: 37926

South Asian (SAS) AF: 0.554 AC: 36663 AN: 66170

European-Finnish (FIN) AF: 0.350 AC: 12644 AN: 36128

Middle Eastern (MID) AF: 0.226 AC: 770 AN: 3404

European-Non Finnish (NFE) AF: 0.326 AC: 296639 AN: 911232

Other (OTH) AF: 0.341 AC: 17141 AN: 50254

GnomAD4 genome AF: 0.312 AC: 47458 AN: 151888 Hom.: 8091 Cov.: 32 AF XY: 0.321 AC XY: 23792 AN XY: 74220

African (AFR) AF: 0.230 AC: 9540 AN: 41430

American (AMR) AF: 0.274 AC: 4177 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 991 AN: 3464

East Asian (EAS) AF: 0.655 AC: 3381 AN: 5162

South Asian (SAS) AF: 0.568 AC: 2732 AN: 4814

European-Finnish (FIN) AF: 0.378 AC: 3983 AN: 10526

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21685 AN: 67926

Other (OTH) AF: 0.272 AC: 571 AN: 2100

Alfa AF: 0.286 Hom.: 2648

Bravo AF: 0.297

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
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.6
DANN	Benign	0.59
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism (auto)

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: rs11172344; hg19: chr12-58193448;