10-126004905-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_145235.5(FANK1):c.561G>A(p.Ala187=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0065 in 1,614,090 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0054 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0066 (46 hom.)
• Consequence: FANK1 NM_145235.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0170

Genes affected

FANK1 (HGNC:23527): (fibronectin type III and ankyrin repeat domains 1) Involved in regulation of apoptotic process and regulation of transcription, DNA-templated. Located in cytosol and nucleoplasm. Colocalizes with chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 10-126004905-G-A is Benign according to our data. Variant chr10-126004905-G-A is described in ClinVar as [Benign]. Clinvar id is 778475.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.017 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FANK1	NM_145235.5	c.561G>A	p.Ala187=	synonymous_variant	7/11	ENST00000368693.6
FANK1	NM_001350939.2	c.639G>A	p.Ala213=	synonymous_variant	8/12
FANK1	NM_001363549.2	c.543G>A	p.Ala181=	synonymous_variant	7/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FANK1	ENST00000368693.6	c.561G>A	p.Ala187=	synonymous_variant	7/11	1	NM_145235.5	P1

Frequencies

GnomAD3 genomes AF: 0.00544 AC: 827 AN: 152126 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00150

Gnomad AMI AF: 0.00549

Gnomad AMR AF: 0.00753

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00415

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.00828

Gnomad OTH AF: 0.00527

GnomAD3 exomes AF: 0.00527 AC: 1326 AN: 251450 Hom.: 7 AF XY: 0.00544 AC XY: 739 AN XY: 135896

Gnomad AFR exome AF: 0.00135

Gnomad AMR exome AF: 0.00532

Gnomad ASJ exome AF: 0.0146

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00480

Gnomad FIN exome AF: 0.000647

Gnomad NFE exome AF: 0.00673

Gnomad OTH exome AF: 0.00766

GnomAD4 exome AF: 0.00661 AC: 9664 AN: 1461846 Hom.: 46 Cov.: 33 AF XY: 0.00656 AC XY: 4774 AN XY: 727214

Gnomad4 AFR exome AF: 0.00137

Gnomad4 AMR exome AF: 0.00570

Gnomad4 ASJ exome AF: 0.0132

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00441

Gnomad4 FIN exome AF: 0.000861

Gnomad4 NFE exome AF: 0.00727

Gnomad4 OTH exome AF: 0.00793

GnomAD4 genome AF: 0.00543 AC: 826 AN: 152244 Hom.: 4 Cov.: 32 AF XY: 0.00485 AC XY: 361 AN XY: 74426

Gnomad4 AFR AF: 0.00149

Gnomad4 AMR AF: 0.00752

Gnomad4 ASJ AF: 0.0127

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00415

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00826

Gnomad4 OTH AF: 0.00522

Alfa AF: 0.00693 Hom.: 2

Bravo AF: 0.00549

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00872

EpiControl AF: 0.00865

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

Invitae

Jun 15, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	0.45
Dann	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs149457380; hg19: chr10-127693474; COSMIC: COSV100904899;