chr12-57801990-C-T

Position:

• chr12-57801990-C-T

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.2151+170G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 152,064 control chromosomes in the GnomAD database, including 10,881 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.36 (10881 hom., cov: 32)
• Consequence: AVIL NM_006576.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.114

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 12-57801990-C-T is Benign according to our data. Variant chr12-57801990-C-T is described in ClinVar as [Benign]. Clinvar id is 1231318.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AVIL	NM_006576.4	c.2151+170G>A		intron_variant		ENST00000549994.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AVIL	ENST00000549994.2	c.2151+170G>A		intron_variant		4	NM_006576.4	P1

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54808 AN: 151946 Hom.: 10886 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.440

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.360 AC: 54790 AN: 152064 Hom.: 10881 Cov.: 32 AF XY: 0.356 AC XY: 26497 AN XY: 74332

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.345

Gnomad4 ASJ AF: 0.532

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.386

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.438

Alfa AF: 0.405 Hom.: 1649

Bravo AF: 0.349

Asia WGS AF: 0.243 AC: 847 AN: 3478

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	6.7
DANN	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3816896; hg19: chr12-58195773; COSMIC: COSV57683260; COSMIC: COSV57683260;