Genetic Variant NM_001003845.3:c.662G>C (chr2-170716869-G-C) – 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.662G>C(p.Arg221Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000152 in 1,318,648 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: not found (cov: 33)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

SP5
NM_001003845.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.41

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:

Genome browser will be placed here

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=0.15507841).

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.662G>C	p.Arg221Pro	missense	Exon 2 of 2	NP_001003845.1	Q6BEB4
	ERICH2-DT	NR_110185.1		n.376+6635C>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SP5	ENST00000375281.4	TSL:1 MANE Select	c.662G>C	p.Arg221Pro	missense	Exon 2 of 2	ENSP00000364430.3	Q6BEB4
ERICH2-DT	ENST00000662274.1		n.859+6635C>G		intron	N/A
ERICH2-DT	ENST00000671292.2		n.387+6635C>G		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000256

AC:

AN:

77988

AF XY:

0.0000224

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000193

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000152

AC:

AN:

1318648

Hom.:

Cov.:

AF XY:

0.00000154

AC XY:

AN XY:

649846

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25640

American (AMR)

AF:

0.0000951

AC:

AN:

21020

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22202

East Asian (EAS)

AF:

0.00

AC:

AN:

29392

South Asian (SAS)

AF:

0.00

AC:

AN:

69362

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3834

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1046528

Other (OTH)

AF:

0.00

AC:

AN:

54080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

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.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.11

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.57

M_CAP

Pathogenic

0.68

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

PhyloP100

1.4

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-1.1

REVEL

Uncertain

0.33

Sift

Benign

0.083

Sift4G

Benign

0.26

Polyphen

0.0010

Vest4

0.26

MutPred

0.22

Gain of glycosylation at R221 (P = 0.0135)

MVP

0.048

ClinPred

0.11

GERP RS

3.4

Varity_R

0.49

gMVP

0.54

Mutation Taster

=39/61

disease causing

(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