Genetic Variant SP5:p.Pro172Leu (chr2-170716722-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001003845.3(SP5):c.515C>T(p.Pro172Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000748 in 1,337,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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. P172R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.5e-7 ( 0 hom. )

Consequence

SP5
NM_001003845.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.340

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08877444).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003845.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP5	NM_001003845.3	MANE Select	c.515C>T	p.Pro172Leu	missense	Exon 2 of 2	NP_001003845.1	Q6BEB4
	ERICH2-DT	NR_110185.1		n.376+6782G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SP5	ENST00000375281.4	TSL:1 MANE Select	c.515C>T	p.Pro172Leu	missense	Exon 2 of 2	ENSP00000364430.3	Q6BEB4
ERICH2-DT	ENST00000662274.1		n.859+6782G>A		intron	N/A
ERICH2-DT	ENST00000671292.2		n.387+6782G>A		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.48e-7

AC:

AN:

1337112

Hom.:

Cov.:

AF XY:

0.00000152

AC XY:

AN XY:

659420

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26712

American (AMR)

AF:

0.00

AC:

AN:

28050

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22932

East Asian (EAS)

AF:

0.00

AC:

AN:

30270

South Asian (SAS)

AF:

0.00

AC:

AN:

73132

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36958

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4044

European-Non Finnish (NFE)

AF:

9.44e-7

AC:

AN:

1059488

Other (OTH)

AF:

0.00

AC:

AN:

55526

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.069

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.56

M_CAP

Uncertain

0.094

MetaRNN

Benign

0.089

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

PhyloP100

-0.34

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.26

REVEL

Benign

0.081

Sift

Benign

0.053

Sift4G

Benign

0.28

Polyphen

0.0020

Vest4

0.28

MutPred

0.33

Loss of glycosylation at P172 (P = 4e-04)

MVP

0.088

ClinPred

0.15

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.079

gMVP

0.37

Mutation Taster

=89/11

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over