rs11390146

Positions:

• chr1-153547779-AC-A
• chr1-153547779-AC-ACC

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_002960.2(S100A3):​c.208delG​(p.Val70fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00481 in 1,613,914 control chromosomes in the GnomAD database, including 30 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0029 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0050 (30 hom.)
• Consequence: S100A3 NM_002960.2 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.44

Genes affected

S100A3 (HGNC:10493): (S100 calcium binding protein A3) 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 has the highest content of cysteines of all S100 proteins, has a high affinity for Zinc, and is highly expressed in human hair cuticle. The precise function of this protein is unknown. [provided by RefSeq, Jul 2008]

S100A4 (HGNC:10494): (S100 calcium binding protein A4) 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. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]

LOC101928034 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
S100A3	NM_002960.2	c.208delG	p.Val70fs	frameshift_variant	3/3	ENST00000368713.8	NP_002951.1
LOC101928034	NR_125947.1	n.169-640delC		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
S100A3	ENST00000368713.8	c.208delG	p.Val70fs	frameshift_variant	3/3	1	NM_002960.2	ENSP00000357702.3
S100A3	ENST00000368712.1	c.208delG	p.Val70fs	frameshift_variant	3/3	3		ENSP00000357701.1
S100A4	ENST00000368714.1	c.-16+2285delG		intron_variant		3		ENSP00000357703.1

Frequencies

GnomAD3 genomes AF: 0.00289 AC: 440 AN: 152008 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00516

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00289 AC: 726 AN: 251420 Hom.: 3 AF XY: 0.00293 AC XY: 398 AN XY: 135876

Gnomad AFR exome AF: 0.000861

Gnomad AMR exome AF: 0.00168

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000554

Gnomad NFE exome AF: 0.00551

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.00501 AC: 7329 AN: 1461788 Hom.: 30 Cov.: 31 AF XY: 0.00486 AC XY: 3537 AN XY: 727212

Gnomad4 AFR exome AF: 0.00131

Gnomad4 AMR exome AF: 0.00204

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.000842

Gnomad4 NFE exome AF: 0.00624

Gnomad4 OTH exome AF: 0.00339

GnomAD4 genome AF: 0.00289 AC: 440 AN: 152126 Hom.: 0 Cov.: 32 AF XY: 0.00253 AC XY: 188 AN XY: 74356

Gnomad4 AFR AF: 0.00106

Gnomad4 AMR AF: 0.00190

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000944

Gnomad4 NFE AF: 0.00516

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00115 Hom.: 0

Bravo AF: 0.00327

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs11390146; hg19: chr1-153520255;