12-108834138-T-C

Variant names:

• chr12-108834138-T-C
• rs2375016
• NM_018984.4:c.111-10777A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000326495.10(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 ENST00000326495.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.992
• Publications: 8 publications found

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]

ENSG00000274598 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000326495.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSH1	NM_018984.4	MANE Select	c.111-10777A>G		intron	N/A	NP_061857.3
	SSH1	NM_001161330.2		c.111-10777A>G		intron	N/A	NP_001154802.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSH1	ENST00000326495.10	TSL:1 MANE Select	c.111-10777A>G		intron	N/A	ENSP00000315713.5
	SSH1	ENST00000551165.5	TSL:1	c.111-10777A>G		intron	N/A	ENSP00000448824.1
	ENSG00000274598	ENST00000612818.1	TSL:6	n.247A>G		non_coding_transcript_exon	Exon 1 of 1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.417 AC: 10 AN: 24

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.360 AC: 14920 AN: 41482

American (AMR) AF: 0.317 AC: 4849 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1390 AN: 3468

East Asian (EAS) AF: 0.432 AC: 2234 AN: 5172

South Asian (SAS) AF: 0.453 AC: 2190 AN: 4830

European-Finnish (FIN) AF: 0.387 AC: 4101 AN: 10586

Middle Eastern (MID) AF: 0.353 AC: 103 AN: 292

European-Non Finnish (NFE) AF: 0.322 AC: 21904 AN: 67994

Other (OTH) AF: 0.349 AC: 739 AN: 2116

Alfa AF: 0.328 Hom.: 13753

Bravo AF: 0.336

Asia WGS AF: 0.476 AC: 1654 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.76
DANN	Benign	0.31
PhyloP100		-0.99
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2375016; hg19: chr12-109227914;