12-57799665-T-C

Position:

• chr12-57799665-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AVIL	NM_006576.4	c.2346+130A>G		intron_variant		ENST00000549994.2	NP_006567.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AVIL	ENST00000549994.2	c.2346+130A>G		intron_variant		4	NM_006576.4	ENSP00000449239	P1

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

Gnomad4 AFR exome AF: 0.215

Gnomad4 AMR exome AF: 0.337

Gnomad4 ASJ exome AF: 0.288

Gnomad4 EAS exome AF: 0.702

Gnomad4 SAS exome AF: 0.554

Gnomad4 FIN exome AF: 0.350

Gnomad4 NFE exome AF: 0.326

Gnomad4 OTH exome AF: 0.341

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

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.655

Gnomad4 SAS AF: 0.568

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.272

Alfa AF: 0.300 Hom.: 1166

Bravo AF: 0.297

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.6
DANN	Benign	0.59

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

LitVar

Other links and lift over

dbSNP: rs11172344; hg19: chr12-58193448;