chr12-108826127-C-G

Position:

• chr12-108826127-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018984.4(SSH1):​c.111-2766G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 454,330 control chromosomes in the GnomAD database, including 9,385 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (4271 hom., cov: 31)
  • Exomes 𝑓: 0.14 (5114 hom.)
• Consequence: SSH1 NM_018984.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.193

Genes affected

SSH1 (HGNC:30579): (slingshot protein phosphatase 1) The protein encoded by this gene belongs to the slingshot homolog (SSH) family of phosphatases, which regulate actin filament dynamics. The SSH proteins dephosphorylate and activate the actin binding/depolymerizing factor cofilin, which subsequently binds to actin filaments and stimulates their disassembly. Cofilin is inactivated by kinases such as LIM domain kinase-1 (LIMK1), which may also be dephosphorylated and inactivated by SSH proteins. The SSH family thus appears to play a role in actin dynamics by reactivating cofilin proteins. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SSH1	NM_018984.4	c.111-2766G>C		intron_variant		ENST00000326495.10	NP_061857.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SSH1	ENST00000326495.10	c.111-2766G>C		intron_variant		1	NM_018984.4	ENSP00000315713	P2

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30523 AN: 151828 Hom.: 4262 Cov.: 31

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.0677

Gnomad FIN AF: 0.0646

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.215

GnomAD3 exomes AF: 0.194 AC: 24570 AN: 126760 Hom.: 3759 AF XY: 0.173 AC XY: 12047 AN XY: 69564

Gnomad AFR exome AF: 0.360

Gnomad AMR exome AF: 0.406

Gnomad ASJ exome AF: 0.200

Gnomad EAS exome AF: 0.351

Gnomad SAS exome AF: 0.0648

Gnomad FIN exome AF: 0.0543

Gnomad NFE exome AF: 0.108

Gnomad OTH exome AF: 0.175

GnomAD4 exome AF: 0.144 AC: 43531 AN: 302386 Hom.: 5114 Cov.: 0 AF XY: 0.132 AC XY: 22752 AN XY: 172388

Gnomad4 AFR exome AF: 0.351

Gnomad4 AMR exome AF: 0.406

Gnomad4 ASJ exome AF: 0.196

Gnomad4 EAS exome AF: 0.346

Gnomad4 SAS exome AF: 0.0690

Gnomad4 FIN exome AF: 0.0632

Gnomad4 NFE exome AF: 0.107

Gnomad4 OTH exome AF: 0.152

GnomAD4 genome AF: 0.201 AC: 30562 AN: 151944 Hom.: 4271 Cov.: 31 AF XY: 0.200 AC XY: 14839 AN XY: 74270

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.329

Gnomad4 SAS AF: 0.0680

Gnomad4 FIN AF: 0.0646

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.213

Alfa AF: 0.0888 Hom.: 183

Bravo AF: 0.236

Asia WGS AF: 0.165 AC: 572 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.2
DANN	Benign	0.62

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: rs6539455; hg19: chr12-109219903;