chr4-6697022-G-A

Variant names:

• chr4-6697022-G-A
• rs775589745
• NM_005980.3:c.268G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005980.3(S100P):​c.268G>A​(p.Glu90Lys) 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. 15/21 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. E90Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: S100P NM_005980.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.179
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046091348).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005980.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	S100P	NM_005980.3	MANE Select	c.268G>A	p.Glu90Lys	missense	Exon 2 of 2	NP_005971.1	P25815

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	S100P	ENST00000296370.4	TSL:1 MANE Select	c.268G>A	p.Glu90Lys	missense	Exon 2 of 2	ENSP00000296370.3	P25815
	S100P	ENST00000513778.1	TSL:3	n.165G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.5
DANN	Benign	0.47
DEOGEN2	Benign	0.050	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-0.93	T
PhyloP100		-0.18
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.016
Sift	Benign	0.36	T
Sift4G	Benign	0.67	T
Polyphen		0.0030	B
Vest4		0.069
MutPred		0.43		Gain of MoRF binding (P = 1e-04)
MVP		0.22
MPC		0.082
ClinPred		0.076	T
GERP RS		-6.0
Varity_R		0.17
gMVP		0.11
Mutation Taster		=87/13	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: rs775589745; hg19: chr4-6698749;