12-57799665-T-C

Variant names:

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

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

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 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 rank	MANE	Protein	UniProt
AVIL	NM_006576.4	c.2346+130A>G		intron_variant	Intron 19 of 19	ENST00000549994.2	NP_006567.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AVIL	ENST00000549994.2	c.2346+130A>G		intron_variant	Intron 19 of 19	4	NM_006576.4	ENSP00000449239.2

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 AC: 5759 AN: 26800

Gnomad4 AMR exome AF: 0.337 AC: 10129 AN: 30050

Gnomad4 ASJ exome AF: 0.288 AC: 5620 AN: 19524

Gnomad4 EAS exome AF: 0.702 AC: 26622 AN: 37926

Gnomad4 SAS exome AF: 0.554 AC: 36663 AN: 66170

Gnomad4 FIN exome AF: 0.350 AC: 12644 AN: 36128

Gnomad4 NFE exome AF: 0.326 AC: 296639 AN: 911232

Gnomad4 Remaining exome 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

Gnomad4 AFR AF: 0.230 AC: 0.230268 AN: 0.230268

Gnomad4 AMR AF: 0.274 AC: 0.273722 AN: 0.273722

Gnomad4 ASJ AF: 0.286 AC: 0.286085 AN: 0.286085

Gnomad4 EAS AF: 0.655 AC: 0.654979 AN: 0.654979

Gnomad4 SAS AF: 0.568 AC: 0.567511 AN: 0.567511

Gnomad4 FIN AF: 0.378 AC: 0.378396 AN: 0.378396

Gnomad4 NFE AF: 0.319 AC: 0.319244 AN: 0.319244

Gnomad4 OTH AF: 0.272 AC: 0.271905 AN: 0.271905

Alfa AF: 0.286 Hom.: 2648

Bravo AF: 0.297

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 10, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs11172344; hg19: chr12-58193448;