10-125980324-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_145235.5(FANK1):c.177T>C(p.Tyr59=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,613,958 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0066 (16 hom., cov: 32)
  • Exomes 𝑓: 0.00076 (10 hom.)
• Consequence: FANK1 NM_145235.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.689

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 10-125980324-T-C is Benign according to our data. Variant chr10-125980324-T-C is described in ClinVar as [Benign]. Clinvar id is 780916.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00656 (999/152316) while in subpopulation AFR AF= 0.0226 (940/41562). AF 95% confidence interval is 0.0214. There are 16 homozygotes in gnomad4. There are 479 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FANK1	NM_145235.5	c.177T>C	p.Tyr59=	synonymous_variant	2/11	ENST00000368693.6
FANK1	NM_001350939.2	c.177T>C	p.Tyr59=	synonymous_variant	2/12
FANK1	NM_001363549.2	c.159T>C	p.Tyr53=	synonymous_variant	2/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FANK1	ENST00000368693.6	c.177T>C	p.Tyr59=	synonymous_variant	2/11	1	NM_145235.5	P1

Frequencies

GnomAD3 genomes AF: 0.00652 AC: 993 AN: 152198 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.0225

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00180 AC: 451 AN: 250972 Hom.: 4 AF XY: 0.00129 AC XY: 175 AN XY: 135658

Gnomad AFR exome AF: 0.0226

Gnomad AMR exome AF: 0.00136

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000984

Gnomad FIN exome AF: 0.000231

Gnomad NFE exome AF: 0.000202

Gnomad OTH exome AF: 0.000653

GnomAD4 exome AF: 0.000764 AC: 1117 AN: 1461642 Hom.: 10 Cov.: 31 AF XY: 0.000656 AC XY: 477 AN XY: 727118

Gnomad4 AFR exome AF: 0.0222

Gnomad4 AMR exome AF: 0.00152

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.000337

Gnomad4 NFE exome AF: 0.000149

Gnomad4 OTH exome AF: 0.00176

GnomAD4 genome AF: 0.00656 AC: 999 AN: 152316 Hom.: 16 Cov.: 32 AF XY: 0.00643 AC XY: 479 AN XY: 74490

Gnomad4 AFR AF: 0.0226

Gnomad4 AMR AF: 0.00183

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00363 Hom.: 3

Bravo AF: 0.00761

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000356

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

Jan 08, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	0.87
Dann	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs147745029; hg19: chr10-127668893;