Variant 2-170716799-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000375281.4(SP5):c.592G>C(p.Gly198Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000474 in 1,391,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

SP5
ENST00000375281.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.46

Variant links:

Genes affected

SP5 (HGNC:14529): (Sp5 transcription factor) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within bone morphogenesis; cellular response to organic cyclic compound; and post-anal tail morphogenesis. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

SP5 links:

ERICH2-DT (HGNC:55686): (ERICH2 divergent transcript)

ERICH2-DT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.25471443).

BS2

High AC in GnomAd4 at 47 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SP5	NM_001003845.3 linkuse as main transcript	c.592G>C	p.Gly198Arg	missense_variant	2/2	ENST00000375281.4	NP_001003845.1
ERICH2-DT	NR_110185.1 linkuse as main transcript	n.376+6705C>G		intron_variant, non_coding_transcript_variant
SP5	XM_005246542.5 linkuse as main transcript	c.724G>C	p.Gly242Arg	missense_variant	2/2		XP_005246599.1
SP5	XM_047444264.1 linkuse as main transcript	c.364G>C	p.Gly122Arg	missense_variant	2/2		XP_047300220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
SP5	ENST00000375281.4 linkuse as main transcript	c.592G>C	p.Gly198Arg	missense_variant	2/2	1	NM_001003845.3	ENSP00000364430	P1
ERICH2-DT	ENST00000662274.1 linkuse as main transcript	n.859+6705C>G		intron_variant, non_coding_transcript_variant
ERICH2-DT	ENST00000671292.1 linkuse as main transcript	n.336+6705C>G		intron_variant, non_coding_transcript_variant
ERICH2-DT	ENST00000690230.1 linkuse as main transcript	n.404+6705C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000310

AC:

AN:

151778

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000153

AC:

AN:

1239382

Hom.:

Cov.:

AF XY:

0.0000149

AC XY:

AN XY:

605950

show subpopulations

Gnomad4 AFR exome

AF:

0.000578

Gnomad4 AMR exome

AF:

0.0000765

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.90e-7

Gnomad4 OTH exome

AF:

0.0000591

GnomAD4 genome

AF:

0.000310

AC:

AN:

151778

Hom.:

Cov.:

AF XY:

0.000297

AC XY:

AN XY:

74134

show subpopulations

Gnomad4 AFR

AF:

0.00106

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000344

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 04, 2023

The c.592G>C (p.G198R) alteration is located in exon 2 (coding exon 2) of the SP5 gene. This alteration results from a G to C substitution at nucleotide position 592, causing the glycine (G) at amino acid position 198 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.47

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.63

DEOGEN2

Benign

0.097

Eigen

Benign

0.16

Eigen_PC

Benign

0.056

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.63

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.25

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

MutationTaster

Benign

0.98

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.58

REVEL

Benign

0.25

Sift

Benign

0.57

Sift4G

Benign

0.49

Polyphen

1.0

Vest4

0.27

MutPred

0.25

Gain of methylation at G198 (P = 0.0093);

MVP

0.16

ClinPred

0.53

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.44

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