chr1-153534787-TC-T

Variant names:

• chr1-153534787-TC-T
• rs2101678002
• NM_014624.4:c.181delG

Variant summary

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

The NM_014624.4(S100A6):​c.181delG​(p.Asp61ThrfsTer8) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000205 in 1,461,626 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: S100A6 NM_014624.4 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.14
• Publications: 0 publications found

Genes affected

S100A6 (HGNC:10496): (S100 calcium binding protein A6) 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 stimulation of Ca2+-dependent insulin release, stimulation of prolactin secretion, and exocytosis. Chromosomal rearrangements and altered expression of this gene have been implicated in melanoma. [provided by RefSeq, Jul 2008]

ENSG00000238279 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014624.4. 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
	S100A6	NM_014624.4	MANE Select	c.181delG	p.Asp61ThrfsTer8	frameshift	Exon 3 of 3	NP_055439.1	P06703

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	S100A6	ENST00000368719.9	TSL:1 MANE Select	c.181delG	p.Asp61ThrfsTer8	frameshift	Exon 3 of 3	ENSP00000357708.3	P06703
	S100A6	ENST00000368720.6	TSL:3	c.181delG	p.Asp61ThrfsTer8	frameshift	Exon 4 of 4	ENSP00000357709.1	P06703
	S100A6	ENST00000496817.5	TSL:2	c.181delG	p.Asp61ThrfsTer8	frameshift	Exon 3 of 3	ENSP00000473589.1	P06703

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461626 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727154

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.000352 AC: 2 AN: 5686

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111930

Other (OTH) AF: 0.0000166 AC: 1 AN: 60376

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2101678002; hg19: chr1-153507263;