1-152032688-C-T

Variant names:

• chr1-152032688-C-T
• NM_005620.2:c.292G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005620.2(S100A11):​c.292G>A​(p.Ala98Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,214 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A98P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: S100A11 NM_005620.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

Genes affected

S100A11 (HGNC:10488): (S100 calcium binding protein A11) 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. This protein may function in motility, invasion, and tubulin polymerization. Chromosomal rearrangements and altered expression of this gene have been implicated in tumor metastasis. [provided by RefSeq, Jul 2008]

ENSG00000229021 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039002).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
S100A11	NM_005620.2	c.292G>A	p.Ala98Thr	missense_variant	Exon 3 of 3	ENST00000271638.3	NP_005611.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
S100A11	ENST00000271638.3	c.292G>A	p.Ala98Thr	missense_variant	Exon 3 of 3	1	NM_005620.2	ENSP00000271638.2
S100A11	ENST00000478109.1	n.375G>A		non_coding_transcript_exon_variant	Exon 3 of 3	3
ENSG00000229021	ENST00000432386.1	n.2920-8897C>T		intron_variant	Intron 12 of 12	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461214 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726832

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

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	Benign	0.071
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.3
DANN	Benign	0.78
DEOGEN2	Benign	0.15	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.90	L
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.010
Sift	Benign	0.38	T
Sift4G	Benign	0.61	T
Polyphen		0.0	B
Vest4		0.068
MutPred		0.26		Gain of phosphorylation at A98 (P = 0.0595);
MVP		0.095
MPC		0.16
ClinPred		0.057	T
GERP RS		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.024
gMVP		0.12

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: chr1-152005164; COSMIC: COSV54975473;