2-174336524-C-T

Variant names:

• chr2-174336524-C-T
• NM_001145250.2:c.439C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001145250.2(SP9):​c.439C>T​(p.Pro147Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000231 in 1,296,674 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. P147T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: SP9 NM_001145250.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.90

Genes affected

SP9 (HGNC:30690): (Sp9 transcription factor) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000280414 (HGNC:):

ACMG classification

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=0.20946205).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP9	NM_001145250.2	c.439C>T	p.Pro147Ser	missense_variant	Exon 2 of 2	ENST00000394967.3	NP_001138722.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SP9	ENST00000394967.3	c.439C>T	p.Pro147Ser	missense_variant	Exon 2 of 2	5	NM_001145250.2	ENSP00000378418.2
ENSG00000280414	ENST00000624790.1	n.1043G>A		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000231 AC: 3 AN: 1296674 Hom.: 0 Cov.: 36 AF XY: 0.00000474 AC XY: 3 AN XY: 633506

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: 0.00000289

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.57
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.2	L
PrimateAI	Pathogenic	0.93	D
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.10
Sift	Benign	0.46	T
Sift4G	Benign	0.88	T
Polyphen		0.54	P
Vest4		0.29
MutPred		0.73		Gain of glycosylation at P147 (P = 0.0157);
MVP		0.040
MPC		1.3
ClinPred		0.46	T
GERP RS		1.2
Varity_R		0.15
gMVP		0.68

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.

Other links and lift over

hg19: chr2-175201252;