rs756696662

Variant names:

• chr7-20784808-G-A
• NM_182700.6:c.1009C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-20784808-G-A
• chr7-20784808-G-C

Variant summary

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

The NM_182700.6(SP8):​c.1009C>T​(p.Pro337Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000726 in 1,377,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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. P337A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: SP8 NM_182700.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.787

Genes affected

SP8 (HGNC:19196): (Sp8 transcription factor) The protein encoded by this gene is an SP family transcription factor that in mouse has been shown to be essential for proper limb development. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2011]

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=0.09515497).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP8	NM_182700.6	c.1009C>T	p.Pro337Ser	missense_variant	Exon 2 of 2	ENST00000418710.3	NP_874359.2
SP8	NM_198956.4	c.955C>T	p.Pro319Ser	missense_variant	Exon 3 of 3		NP_945194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SP8	ENST00000418710.3	c.1009C>T	p.Pro337Ser	missense_variant	Exon 2 of 2	1	NM_182700.6	ENSP00000408792.2
SP8	ENST00000361443.4	c.955C>T	p.Pro319Ser	missense_variant	Exon 3 of 3	1		ENSP00000354482.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.26e-7 AC: 1 AN: 1377516 Hom.: 0 Cov.: 37 AF XY: 0.00000147 AC XY: 1 AN XY: 679942

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: 9.29e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	.;.;T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.28
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.82	T;T;T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.095	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.38	.;.;N
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-2.7	.;D;N
REVEL	Benign	0.18
Sift	Benign	0.30	.;T;T
Sift4G	Benign	0.37	T;T;T
Polyphen		0.024	.;.;B
Vest4		0.095
MutPred		0.33		.;.;Gain of phosphorylation at P319 (P = 0.0035);
MVP		0.18
ClinPred		0.43	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.28
gMVP		0.69

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: chr7-20824427;