chr4-6696929-A-G

Position:

• chr4-6696929-A-G

Variant summary

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

The NM_005980.3(S100P):​c.175A>G​(p.Lys59Glu) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 35)
• Consequence: S100P NM_005980.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.775

Genes affected

S100P (HGNC:10504): (S100 calcium binding protein P) The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S100 genes include at least 13 members which are located as a cluster on chromosome 1q21; however, this gene is located at 4p16. This protein, in addition to binding Ca2+, also binds Zn2+ and Mg2+. This protein may play a role in the etiology of prostate cancer. [provided by RefSeq, Jul 2008]

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=0.10433018).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
S100P	NM_005980.3	c.175A>G	p.Lys59Glu	missense_variant	2/2	ENST00000296370.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
S100P	ENST00000296370.4	c.175A>G	p.Lys59Glu	missense_variant	2/2	1	NM_005980.3	P1
S100P	ENST00000513778.1	n.72A>G		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 35

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 11, 2022

The c.175A>G (p.K59E) alteration is located in exon 2 (coding exon 2) of the S100P gene. This alteration results from a A to G substitution at nucleotide position 175, causing the lysine (K) at amino acid position 59 to be replaced by a glutamic acid (E). 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	Benign	0.32
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.082	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	0.86	N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.017
Sift	Benign	0.061	T
Sift4G	Uncertain	0.042	D
Polyphen		0.12	B
Vest4		0.097
MutPred		0.41		Loss of ubiquitination at K59 (P = 0.0174);
MVP		0.40
MPC		0.13
ClinPred		0.95	D
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.37
gMVP		0.25

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: chr4-6698656;