2-170716412-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_ModerateBS2

The NM_001003845.3(SP5):​c.205C>T​(p.Leu69Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000345 in 1,447,962 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: 0.0000035 ( 0 hom. )

Consequence

SP5
NM_001003845.3 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.419
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]
ERICH2-DT (HGNC:55686): (ERICH2 divergent transcript)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09906319).
BS2
High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SP5NM_001003845.3 linkc.205C>T p.Leu69Phe missense_variant Exon 2 of 2 ENST00000375281.4 NP_001003845.1 Q6BEB4
SP5XM_005246542.5 linkc.337C>T p.Leu113Phe missense_variant Exon 2 of 2 XP_005246599.1
SP5XM_047444264.1 linkc.-24C>T 5_prime_UTR_variant Exon 2 of 2 XP_047300220.1
ERICH2-DTNR_110185.1 linkn.376+7092G>A intron_variant Intron 5 of 5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SP5ENST00000375281.4 linkc.205C>T p.Leu69Phe missense_variant Exon 2 of 2 1 NM_001003845.3 ENSP00000364430.3 Q6BEB4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000447
AC:
1
AN:
223614
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
124674
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000994
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000345
AC:
5
AN:
1447962
Hom.:
0
Cov.:
41
AF XY:
0.00000277
AC XY:
2
AN XY:
720766
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:
0.0000349
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 19, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.205C>T (p.L69F) alteration is located in exon 2 (coding exon 2) of the SP5 gene. This alteration results from a C to T substitution at nucleotide position 205, causing the leucine (L) at amino acid position 69 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
0.56
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
22
DANN
Uncertain
0.98
DEOGEN2
Benign
0.14
T
Eigen
Benign
-0.61
Eigen_PC
Benign
-0.48
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.83
T
M_CAP
Uncertain
0.23
D
MetaRNN
Benign
0.099
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.4
L
PrimateAI
Pathogenic
0.91
D
PROVEAN
Benign
-1.5
N
REVEL
Benign
0.031
Sift
Benign
0.14
T
Sift4G
Benign
0.38
T
Polyphen
0.019
B
Vest4
0.11
MutPred
0.22
Loss of catalytic residue at L69 (P = 0.1246);
MVP
0.081
ClinPred
0.18
T
GERP RS
1.1
Varity_R
0.13
gMVP
0.27

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs761813037; hg19: chr2-171572922; API