chr12-108834138-T-C

Position:

• chr12-108834138-T-C

Variant summary

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

The NM_018984.4(SSH1):​c.111-10777A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,160 control chromosomes in the GnomAD database, including 9,230 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 0.35 (9227 hom., cov: 33)
  • Exomes 𝑓: 0.39 (3 hom.)
• Consequence: SSH1 NM_018984.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.992

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SSH1	NM_018984.4	c.111-10777A>G		intron_variant		ENST00000326495.10	NP_061857.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SSH1	ENST00000326495.10	c.111-10777A>G		intron_variant		1	NM_018984.4	ENSP00000315713	P2
SSH1	ENST00000551165.5	c.111-10777A>G		intron_variant		1		ENSP00000448824	A2
	ENST00000612818.1	n.247A>G		non_coding_transcript_exon_variant	1/1
SSH1	ENST00000548522.5	c.111-15825A>G		intron_variant, NMD_transcript_variant		3		ENSP00000448586

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52588 AN: 152014 Hom.: 9218 Cov.: 33

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.346

GnomAD4 exome AF: 0.393 AC: 11 AN: 28 Hom.: 3 Cov.: 0 AF XY: 0.417 AC XY: 10 AN XY: 24

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.417

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.346 AC: 52637 AN: 152132 Hom.: 9227 Cov.: 33 AF XY: 0.351 AC XY: 26108 AN XY: 74356

Gnomad4 AFR AF: 0.360

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.453

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.322

Gnomad4 OTH AF: 0.349

Alfa AF: 0.328 Hom.: 11037

Bravo AF: 0.336

Asia WGS AF: 0.476 AC: 1654 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.76
DANN	Benign	0.31

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: rs2375016; hg19: chr12-109227914;