Genetic Variant SP8:p.Leu495Leu (chr7-20784332-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2

The NM_182700.6(SP8):c.1485G>A(p.Leu495Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00266 in 1,506,670 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 5 hom. )

Consequence

SP8
NM_182700.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.01

Variant links:

Genes affected

SP8 (HGNC:19196): (Sp8 transcription factor) The protein encoded by this gene is an SP family transcription factor that in mouse has been shown to be essential for proper limb development. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2011]

SP8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 7-20784332-C-T is Benign according to our data. Variant chr7-20784332-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3042795.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=1.01 with no splicing effect.

BS2

High AC in GnomAd4 at 231 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP8	NM_182700.6 link	c.1485G>A	p.Leu495Leu	synonymous_variant	Exon 2 of 2	ENST00000418710.3	NP_874359.2	Q8IXZ3-4A8K350
SP8	NM_198956.4 link	c.1431G>A	p.Leu477Leu	synonymous_variant	Exon 3 of 3		NP_945194.1	Q8IXZ3-3A8K350

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SP8	ENST00000418710.3 link	c.1485G>A	p.Leu495Leu	synonymous_variant	Exon 2 of 2	1	NM_182700.6	ENSP00000408792.2		Q8IXZ3-4
SP8	ENST00000361443.4 link	c.1431G>A	p.Leu477Leu	synonymous_variant	Exon 3 of 3	1		ENSP00000354482.4		Q8IXZ3-3

Frequencies

GnomAD3 genomes

AF:

0.00152

AC:

231

AN:

151982

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000580

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000661

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00249

Gnomad OTH

AF:

0.00336

GnomAD3 exomes

AF:

0.00140

AC:

150

AN:

107482

Hom.:

AF XY:

0.00135

AC XY:

AN XY:

59950

show subpopulations

Gnomad AFR exome

AF:

0.00125

Gnomad AMR exome

AF:

0.000860

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000505

Gnomad FIN exome

AF:

0.000355

Gnomad NFE exome

AF:

0.00307

Gnomad OTH exome

AF:

0.000308

GnomAD4 exome

AF:

0.00279

AC:

3782

AN:

1354578

Hom.:

Cov.:

AF XY:

0.00265

AC XY:

1770

AN XY:

668326

show subpopulations

Gnomad4 AFR exome

AF:

0.000391

Gnomad4 AMR exome

AF:

0.00102

Gnomad4 ASJ exome

AF:

0.0000415

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000131

Gnomad4 FIN exome

AF:

0.00107

Gnomad4 NFE exome

AF:

0.00335

Gnomad4 OTH exome

AF:

0.00213

GnomAD4 genome

AF:

0.00152

AC:

231

AN:

152092

Hom.:

Cov.:

AF XY:

0.00139

AC XY:

103

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.000578

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000661

Gnomad4 NFE

AF:

0.00249

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00214

Hom.:

Bravo

AF:

0.00172

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

SP8-related disorder

Benign:1

Jun 21, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SP8: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.97

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over