11-63818277-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_138471.3(SPINDOC):c.519C>T(p.Ala173=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00157 in 1,613,968 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00097 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0016 (3 hom.)
• Consequence: SPINDOC NM_138471.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.77

Genes affected

SPINDOC (HGNC:25115): (spindlin interactor and repressor of chromatin binding) Involved in negative regulation of transcription, DNA-templated. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 11-63818277-C-T is Benign according to our data. Variant chr11-63818277-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2641904.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.78 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPINDOC	NM_138471.3	c.519C>T	p.Ala173=	synonymous_variant	3/6	ENST00000294244.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPINDOC	ENST00000294244.9	c.519C>T	p.Ala173=	synonymous_variant	3/6	1	NM_138471.3	P1

Frequencies

GnomAD3 genomes AF: 0.000974 AC: 148 AN: 151964 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00182

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000855 AC: 215 AN: 251468 Hom.: 0 AF XY: 0.000898 AC XY: 122 AN XY: 135914

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00174

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.00163 AC: 2379 AN: 1461888 Hom.: 3 Cov.: 32 AF XY: 0.00161 AC XY: 1168 AN XY: 727248

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.000179

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.000206

Gnomad4 NFE exome AF: 0.00200

Gnomad4 OTH exome AF: 0.00217

GnomAD4 genome AF: 0.000973 AC: 148 AN: 152080 Hom.: 0 Cov.: 31 AF XY: 0.000821 AC XY: 61 AN XY: 74338

Gnomad4 AFR AF: 0.000313

Gnomad4 AMR AF: 0.000393

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00182

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00143 Hom.: 0

Bravo AF: 0.000820

EpiCase AF: 0.00185

EpiControl AF: 0.00101

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

SPINDOC: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
Cadd	Benign	0.50
Dann	Benign	0.64

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: rs148120037; hg19: chr11-63585749;