Variant 2-170716845-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001003845.3(SP5):c.638G>T(p.Cys213Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SP5
NM_001003845.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.96

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=0.20126781).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SP5	NM_001003845.3 linkuse as main transcript	c.638G>T	p.Cys213Phe	missense_variant	2/2	ENST00000375281.4	NP_001003845.1
ERICH2-DT	NR_110185.1 linkuse as main transcript	n.376+6659C>A		intron_variant, non_coding_transcript_variant
SP5	XM_005246542.5 linkuse as main transcript	c.770G>T	p.Cys257Phe	missense_variant	2/2		XP_005246599.1
SP5	XM_047444264.1 linkuse as main transcript	c.410G>T	p.Cys137Phe	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.638G>T	p.Cys213Phe	missense_variant	2/2	1	NM_001003845.3	ENSP00000364430	P1
ERICH2-DT	ENST00000662274.1 linkuse as main transcript	n.859+6659C>A		intron_variant, non_coding_transcript_variant
ERICH2-DT	ENST00000671292.1 linkuse as main transcript	n.336+6659C>A		intron_variant, non_coding_transcript_variant
ERICH2-DT	ENST00000690230.1 linkuse as main transcript	n.404+6659C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1286222

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

632244

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Jan 26, 2022

The c.638G>T (p.C213F) alteration is located in exon 2 (coding exon 2) of the SP5 gene. This alteration results from a G to T substitution at nucleotide position 638, causing the cysteine (C) at amino acid position 213 to be replaced by a phenylalanine (F). 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

0.36

BayesDel_addAF

Benign

-0.082

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Benign

0.85

DEOGEN2

Benign

0.12

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.35

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.45

M_CAP

Pathogenic

0.35

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.86

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.70

REVEL

Benign

0.18

Sift

Uncertain

0.010

Sift4G

Uncertain

0.031

Polyphen

0.16

Vest4

0.25

MutPred

0.26

Gain of helix (P = 0.132);

MVP

0.067

ClinPred

0.27

GERP RS

3.8

Varity_R

0.41

gMVP

0.53

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