dbSNP rs1207033358: SP5:p.Pro112Ala (chr2-170716541-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001003845.3(SP5):c.334C>G(p.Pro112Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P112S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SP5
NM_001003845.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.25

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24740523).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP5	NM_001003845.3 link	c.334C>G	p.Pro112Ala	missense_variant	Exon 2 of 2	ENST00000375281.4	NP_001003845.1	Q6BEB4
SP5	XM_005246542.5 link	c.466C>G	p.Pro156Ala	missense_variant	Exon 2 of 2		XP_005246599.1
SP5	XM_047444264.1 link	c.106C>G	p.Pro36Ala	missense_variant	Exon 2 of 2		XP_047300220.1
ERICH2-DT	NR_110185.1 link	n.376+6963G>C		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SP5	ENST00000375281.4 link	c.334C>G	p.Pro112Ala	missense_variant	Exon 2 of 2	1	NM_001003845.3	ENSP00000364430.3		Q6BEB4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1458832

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725688

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.56

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.66

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.33

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.87

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.25

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.098

Sift

Benign

0.088

Sift4G

Uncertain

0.046

Polyphen

0.075

Vest4

0.34

MutPred

0.28

Gain of helix (P = 0.0093);

MVP

0.048

ClinPred

0.95

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.24

gMVP

0.42

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over