2-170716727-A-C

Variant names:

• chr2-170716727-A-C
• rs1414669011
• NM_001003845.3:c.520A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001003845.3(SP5):​c.520A>C​(p.Thr174Pro) 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. 15/22 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. T174A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SP5 NM_001003845.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.482
• Publications: 0 publications found

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)

ACMG classification

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=0.08584088).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP5	NM_001003845.3	c.520A>C	p.Thr174Pro	missense_variant	Exon 2 of 2	ENST00000375281.4	NP_001003845.1
SP5	XM_005246542.5	c.652A>C	p.Thr218Pro	missense_variant	Exon 2 of 2		XP_005246599.1
SP5	XM_047444264.1	c.292A>C	p.Thr98Pro	missense_variant	Exon 2 of 2		XP_047300220.1
ERICH2-DT	NR_110185.1	n.376+6777T>G		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SP5	ENST00000375281.4	c.520A>C	p.Thr174Pro	missense_variant	Exon 2 of 2	1	NM_001003845.3	ENSP00000364430.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	12
DANN	Benign	0.70
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.67
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.34	N
PhyloP100		0.48
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.083
Sift	Benign	0.28	T
Sift4G	Benign	0.075	T
Polyphen		0.49	P
Vest4		0.10
MVP		0.081
ClinPred		0.27	T
GERP RS		-0.73
Varity_R		0.20
gMVP		0.22
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

dbSNP: rs1414669011; hg19: chr2-171573237;