Genetic Variant SP8:p.Ser418Ser (chr7-20784563-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_182700.6(SP8):c.1254C>T(p.Ser418Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000752 in 1,599,460 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.00052 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00078 ( 16 hom. )

Consequence

SP8
NM_182700.6 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.386

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 7-20784563-G-A is Benign according to our data. Variant chr7-20784563-G-A is described in ClinVar as [Benign]. Clinvar id is 3043995.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.386 with no splicing effect.

BS2

High AC in GnomAd4 at 79 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP8	NM_182700.6 link	c.1254C>T	p.Ser418Ser	synonymous_variant	Exon 2 of 2	ENST00000418710.3	NP_874359.2	Q8IXZ3-4A8K350
SP8	NM_198956.4 link	c.1200C>T	p.Ser400Ser	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.1254C>T	p.Ser418Ser	synonymous_variant	Exon 2 of 2	1	NM_182700.6	ENSP00000408792.2		Q8IXZ3-4
SP8	ENST00000361443.4 link	c.1200C>T	p.Ser400Ser	synonymous_variant	Exon 3 of 3	1		ENSP00000354482.4		Q8IXZ3-3

Frequencies

GnomAD3 genomes

AF:

0.000519

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0120

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00183

AC:

408

AN:

223252

Hom.:

AF XY:

0.00244

AC XY:

297

AN XY:

121848

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000343

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0133

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000131

Gnomad OTH exome

AF:

0.000712

GnomAD4 exome

AF:

0.000777

AC:

1124

AN:

1447114

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

811

AN XY:

719060

show subpopulations

Gnomad4 AFR exome

AF:

0.0000903

Gnomad4 AMR exome

AF:

0.000257

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000256

Gnomad4 SAS exome

AF:

0.0114

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000777

Gnomad4 OTH exome

AF:

0.000802

GnomAD4 genome

AF:

0.000519

AC:

AN:

152346

Hom.:

Cov.:

AF XY:

0.000711

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0000721

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0120

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000134

Hom.:

Bravo

AF:

0.000155

Asia WGS

AF:

0.00289

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SP8-related disorder

Benign:1

Mar 20, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

8.0

DANN

Benign

0.95

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